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International Journal of Genetics and Molecular Biology Vol. 3(11), pp. 161-184, December 2011 Available online at http://www.academicjournals.org/ijgmb ISSN2006-9863 ©2012 Academic Journals DOI: 10.5897/IJGMB11.019

Full length Research Paper

Main chromosome aberrations among 4617 chromosomal studies at a third level pediatric Mexican

hospital in 19 years period of time

Aparicio-Rodríguez J. M.1,13, Hurtado-Hernández M. D. L.2, Marroquín-García I.2, Rojas-Rivera G. A.2, Barrientos-Pérez M.3, Gil-Orduña N. C.4,13, Flores-Núñez A.5 , Ruiz-González R.6, Gómez-Tello H.7, Rodríguez-Peralta S.8, Zamudio-Meneses R.9,

Cuellar-López F.10, Cubillo-León M. A.11, Sierra-Pineda F.12, Palma-Guzmán M.13

Chavez-Ozeki H.13 and Chatelain-Mercado S.14

1Department of Genetics, Benemérita Universidad Autónoma de Puebla México. 2Department of Cytogenetics, Benemérita Universidad Autónoma de Puebla México.

3Department of Endocrinology, Benemérita Universidad Autónoma de Puebla México. 4Department of Estomatology, Benemérita Universidad Autónoma de Puebla México.

5Department of Neumology, Benemérita Universidad Autónoma de Puebla México. 6Department of Rheumatology, Benemérita Universidad Autónoma de Puebla México.

7Department of Allergology, Benemérita Universidad Autónoma de Puebla México. 8Department of Neurosurgery, Benemérita Universidad Autónoma de Puebla México.

9Department of Cardiology, Benemérita Universidad Autónoma de Puebla México. 10Department of Urology, Benemérita Universidad Autónoma de Puebla México.

11Department of Physical and ocupational therapy, Benemérita Universidad Autónoma de Puebla México. 12Hospital para el Niño Poblano, Genetics Hospital de la Mujer S.S.A Puebla, Benemérita Universidad Autónoma de

Puebla México. 13Department of Estomatology, Benemérita Universidad Autónoma de Puebla, México.

14Department of Biotechnology, Universidad Autonoma Metropolitana, México.

Accepted 14 November, 2011

Mutations or chromosome aberrations are considered alterations in the chromosome number or structure. They are mainly considered due to gametogenesis inborn error (meiosis) or during the zygote first cellular divisions. All these alterations might be observed during metaphase from the cellular cycle, where DNA loses are seen (clastogenic processes) due to DNA repair processes deficiency o total absence, among others. 4617 chromosomal studies were performed at Hospital Para El Niño Poblano (Pediatric Hospital) in Mexico. During 19 years period of time (from 1992 to 2011) were 34.6% (1596 patients) showed different chromosomal alterations. Among the studies population, male and female pediatric patients with different genetic diseases were chosen. These chromosome changes are classified as numeric or structural alterations, respectively. Another group of genetic alterations are known as mutations and can be inherited among generations. A wide variety of pediatric patients with genetic diseases due to chromosome aberrations are described in this study analyzing their clinical characteristics, medical or surgical treatments and their medical evolution according to the genetic disease. Key words: Chromosome, mutation, chromosome aberration, numeric and structural changes, karyotype and DNA.

INTRODUCTION The word chromosome comes from the Greek (chroma, color) and (soma, body) due to their property of being

strongly stained by particular dyes. A chromosome is an organized structure of DNA and protein found inside

162 Int. J. Genet. Mol. Biol. cells. It is a single piece of coiled DNA with many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions (Thanbichler et al., 2005; Sandman et al., 1998; Sandman and Reeve, 2000; Pereira et al., 1997).

Chromosomes are different according to a variety of organisms. The DNA molecule may be circular or linear, and can be composed of 100,000 to 10,000,000,000 (Paux et al., 2008) nucleotides in a long chain. Normally, eukaryotic cells (cells with nuclei) (White, 1973) have large linear chromosomes and prokaryotic cells (cells without defined nuclei) (Thanbichler and Shapiro, 2006; Nakabachi et al., 2006; Pradella et al., 2002) have smaller circular chromosomes. Also, cells may contain more than one type of chromosome; for example, mitochondria in most eukaryotes and chloroplasts in plants have their own small chromosomes.

In eukaryotes, nuclear chromosomes are packaged by proteins into a condensed structure known as chromatin. This allows the entire DNA molecules to fit into the cell nucleus. The structure of chromosomes and chromatin varies through the cell cycle. Chromosomes are the essential unit for cellular division and must have replication, division, and passed successfully to their daughter cells so as to ensure the genetic diversity and survival of their progeny. Chromosomes may exist as either duplicated or unduplicated. Unduplicated chromosomes are single linear strands, whereas duplicated chromosomes (copied during synthesis phase) contain two copies joined by a centromere. Compaction of the duplicated chromosomes during mitosis and meiosis results in the classic known four-arm structure. Chromosome recombination plays a vital role in evolution and genetic diversity (Hinnebusch and Tilly, 1993).

If these structures begin through processes known as chromosomal instability and mutation, the cell may die, or it may avoid apoptosis leading to initiation of cancer.

Human’s chromosomes are divided into two known types; autosomes, and sex chromosomes. Certain genetic traits are linked to a person's sex, and are passed on through the sex chromosomes. The autosomes contain all the genetic hereditary information. Both chromosome types act in the same way during cell division. Human cells have 23 pairs of large linear nuclear chromosomes (22 pairs of autosomes and one pair of sex chromosomes), giving a total of 46 per cell (Tjio and Levan, 1956). In addition to these, human cells have many hundreds of copies of the mitochondrial genome. The 23 human chromosome during prometaphase in fibroblast cells.

Asexually reproducing species have one set of chromosomes, which are the same in all body cells. However, asexual species can be either haploid or diploid. *Corresponding author. E-mail: jmapar@prodigy,net.mx.

Sexually reproducing species have somatic cells (body cells), which are diploid [2n] having two sets of chromosomes, one from the mother and one from the father. Gametes, reproductive cells, are haploid [n]: They have one set of chromosomes. Gametes are produced by meiosis of a diploid germ line cell (Kelman and Kelman, 2004). During meiosis, the matching chromosomes of father and mother can exchange small parts of themselves (crossover), and thus create new chromosomes that are not inherited solely from either parent. When a male and a female gamete is produced (fertilization), a new diploid organism is then made.

Some animal and plant species are polyploid [Xn]: They have more than two sets of homologous chromosomes. Plants important in agriculture such as tobacco or wheat are often polyploid, compared to their ancestral species. Wheat has a haploid number of seven chromosomes, still seen in some cultivars as well as the wild progenitors. The more-common pasta and bread wheats are polyploid, having 28 (tetraploid) and 42 (hexaploid) chromosomes, compared to the 14 (diploid) chromosomes in the wild wheat (Sakamura, 1918). Therefore, the karyotype is the characteristic chromosome complement of eukaryote organisms. The preparation and study of karyotypes is part of a science called cytogenetics (White, 1973). MATERIALS AND METHODS Chromosomal studies (karyotypes) where performed for all patients in this study by using GTG banding. 4617 karyotypes were performed at Hospital Para el Niño Poblano, Mexico in 19 years period of time (from 1992 to 2011). However, only 1596 patients (34.6%) showed chromosomal alterations, among the studies population, male and female pediatric patients with different genetic diseases were analyzed.

Although, replication and transcription of DNA is highly standardized in eukaryotes, the same cannot be said for their karyotypes, which were often highly variable. There was significant variation between patients in this study, in chromosome number and in detailed organization (mutations); variation between the two sexes, variation between the germ-line and soma (between gametes and the different families). Variation between members Mexican population, due to balanced genetic polymorphism, family’s variation and mosaics or otherwise abnormal individuals. Also, variation in karyotype occurred according to the technique of karyotyping. Cells were locked part-way through division (in metaphase) in vitro (in a reaction vial) with colchicine. These cells were then stained, photographed, and them arranged and evaluated for chromosomal analysis and diagnosis.

DISCCUSSION Chromosomal aberrations are disruptions in the normal chromosomal structures of a cell and are a major cause of genetic conditions in humans, known as genetic disease which might have or not an inheritance pattern, such as Down syndrome, considered as the more frequent chromosomal trisomy observed in this study with

1511 patients (Table 1 and Figure 36). Investigation into the human karyotype took many years to settle the most basic question. How many chromosomes does a normal diploid human cell contain? Hans (1912) reported 47 chromosomes in spermatogonia and 48 in oogonia, concluding an XX/XO sex determination mechanism

(Von, 1912). Painter (1922) was not certain whether the diploid number of man is 46 or 48, at first favoring 46. He revised his opinion later from 46 to 48, and he correctly insisted on humans having an XX/XY system (Painter, 1923; Tjio and Levan, 1956; Ford and Hamerton, 1956).

Considering the techniques of Von (1912) and Painter (1922), their results were quite remarkable. Hsu (1979) showed in chimpanzees (the closest living relatives to modern humans) have 48 chromosomes. Some chromosome abnormalities do not cause disease in carriers, such as translocations, or chromosomal inversions, although they may lead to a higher chance of birthing a child with a chromosome disorder as was found in this study (Table 1). Among the studies population, male and female pediatric patients with different genetic diseases were observed at the department of genetics.

Chromosomal aberrations in this study were analyzed from chromosome 1 to chromosome 22 and then sexual chromosomes. From 4617 karyotypes performed from 1992 to 2011, 34.6% (1596 patients) Figure 34, Table 1 showed chromosomal alterations. However, 33.6% (1553 patients) (Table 1 and Figure 35) have a chromosomal trisomy. From these, 33.6% trisomic population, 32.8% (1511 patients) were diagnosed as Down syndrome (trisomy 21) (Figure 36) and 0.90% has other kind of trisomies (Table 1). Similar as the rest of chromosomal aberrations, 0.93% (43 patients) (Table 1 and Figure 35).

Finally, a diversity of pediatric patients with phenotypical malformations was evaluated during 19 years at the department of genetics. In relation to chromosomal translocations; a male patient with several oral tumors, diagnosed by oral hystopatological studies as Cementoma Gigantiforme (and been evaluated every 6 months by oncology to avoid cellular metastasis) had unexpected balance translocation 46, XY, t (1; 4) (q11q11) (Figure 1 A and B) (Aparicio et al., 2002, 2006). This case is different from a female patient with several abortion processes in her medical background with non cranio-facial alterations (Figure 2 A, B and C), with a chromosomal translocation t (2; 18). Another female patient diagnosed as Opitz G/B.B.B. syndrome Figure 3 A and B. with hypertelorism, unilateral cleft lip and palate and facial asymmetry had unexpected translocation between long arms of chromosomes 3 and 4, 46XX t (3q; 4q) (Aparicio et al., 2011). A male patient with hypertelorism, sinofris, small nose and hypoplasia of nasal wings was also analyzed with a translocation from short arm of chromosome 6 to long arm of chromosome 9 t (6; 9) (Figure 7 A, B and C), which is has been associated to cancer predisposition (Aparicio et al., 2006).

Aparicio-Rodríguez et al. 163

Two healthy carriers parents were observed in this study, one of them (Figure 8 A and B), a healthy carrier mother with translocation 46XX, ins (10; 7) (q21; q23q35) (Figure 8 C and D). However, her mentally retarded son revealed a translocation from long arm of chromosome 10 t (10q+), giving rise to partial trisomy 7 (Aparicio et al., 2010). Similar case as the healthy carrier father (Figure 12 A and B). With a balanced translocation 46XY, ins (10; 9 and his son) (Figure 12 B, C and D), presented plagiocephaly and facial hemiatrophy wide nose and hipoplasic jaw with chromosomal translocation t (9; 10) giving rise to partial trisomy 9. These both families were compared to a family (Figure 17 A, B and C), where a non healthy carrier mother and both son and daughter with none phenotypical malformations. The mother was diagnosed with breast cancer and mastectomy was performed. The family karyotype revealed in all members (mother, son and daughter), translocation between chromosomes 13 and 15 t (13; 15), were cancer has also been associated to this specific chromosomal aberration (Aparicio et al., 2006).

Several patients were diagnosed with bilateral cleft lip and palate and cranio-facial dimorphism like the male patient that revealed a partial trisomy of chromosome 14, (14q24 leads to qter) due to a balance malformation translocation t (11; 14) (q25; q24.1) (Figure 14 A and B) where chromosome 11 is associated to several syndromes (Grossfeld et al., 2004). Similar case as the new born female patient with cleft palate and displasic ears with a balanced chromosomal translocation 21;14 due to a 14 trisomy (Figure 18 A, B and C).

Several patients with facial asymmetry associated to chromosome 16 were observed, for example, two cases where a male patient with cranio-facial dimorphism diagnosed as Parry Romber syndrome and chromosome duplication of the long arm of chromosome 16 (16q+) (Figure 19 A and B). Aparicio et al. (2005) reported similar chromosome findings with a female patient. However, instead of phenotypical malformations, obesity and mental retardation were the main clinical findings, which karyotype revealed a duplication on the hetrocomatic region of chromosome 16 46, XX16 qh+ chromosome 21 (46, XX, 16qh+, 21PSTK+) (Figure 20 A, B and C).

From a total of 4617 karyotypes (100%) performed, 33.6% (1553 patients) (Table 1) were diagnosed as chromosomal trisomy, were 32.8% (1511 patients) (Figure 36) diagnosed as Down syndrome (trisomy 21). This alteration is usually caused by an extra copy of chromosome 21 (trisomy 21). Characteristics include decreased muscle tone, stockier build, asymmetrical skull, slanting eyes and mild to moderate developmental disability (Miller, 2000; Aparicio et al., 2009). 1127 patients have regular trisomy (47XX+21 or 47XY+21) in this study, caused by a meiotic nodisjunction event (Table 1 and Figure 23 A, B and C), also chromosomal translocations were observed; 260 patients 46XYt

164 Int. J. Genet. Mol. Biol.

Table 1. Different chromosomal alteration in 19 years at the Hospital Para el Nino Poblano, Mexico.

Chromosomal aberration (%) patients

1. Trisomy 1553 2. Deletion 9 3. Invertion 1 4. Ring 4 5. Duplication 2 6. Translocation 11 7. Monosomy 15 8. Chimera 1 Chromosomal aberrations (34.6%) 1596 Total Trisomies (33.6%) 1553 A-Trisomy 21 (32.8%) 1511 1. T 21 1127 2. T21;14 260 3. T21;21 43 4. Mosaicism 81 B-Various Trisomies: (0.90%) 42 Different chromosomal aberrations: (0.93%) 43 Total (karyotype studies in 19 years) (100%) 4617 Total normal karyotypes (65.4%) 3021 Total chromosomal aberrations (34.6%) 1596 Chromosomal aberration (%) patients

Figure 1. A. Male patient diagnosed hystopatology as Cementoma Gigantiforme. B. Karyotype shows a balance translocation 46,XY,t(1;4)(q11q11).

21) or 46XXt (14; 21q) were the long arm of chromosome 21 is attached to chromosome 14 (Figure 24 A, B and C), 43 patients 46XYt (21; 21) or 46XXt (21; 21), and 81 patients with mosaicism. Moreover, 0.90% have other kind of trisomies in different chromosomes (Table 1) as

the case of complete trisomy at chromosome 6 in a female patient diagnosed without any phenotypical malformations nor cranio-facial dimorphism (Figure 6 A, B and C), taking in consideration that trisomy 6 is an extremely rare chromosomal disorder and has been

A B


Figure 2. Female patient with several abortion processes, with none A. B. cranio-facial dimorphism C. Karyotype shows a chromosomal translocation t (2;18).

associated to aplastic anemia (Geraedts and Haak, 1976). Partial trisomy of chromosome 7, 46XY, 7q+ was diagnosed in a male patient with facial hypoplasia, narrow set eyes, sinofris, hipoplasic jaw with restricted motion and limited mouth opening (Figure 9 A, B and C) if compared to a female patient with a facial hypoplasia and oblicua desviation of both eyes, small mouth hipoplasic jaw and facial with a partial trisomy of chromosome 7, 46XX, 7q+ (Figure 10 A, B and C).

Edwards and Patau syndromes rarely found among pediatric patients. Both syndromes share similar symptoms. Figure 16 A, B and C shows a female patient

with 13 chromosome trisomy or Patau syndrome with hypoplasic face, bilateral cleft lip and palate and cranio-facial dimorphism, absent or malformed nose especial flexion of the fingers on both hands. Trisomy 13 is the least common of the autosomal trisomies, after Down syndrome (Trisomy 21) and Edwards’s syndrome (Trisomy 18). The extra copy of chromosome 13 in Patau syndrome causes severe neurological and heart defects which make it difficult for infants to survive. In relation to Edwards’s syndrome, a male patient with hirsutism, microcephaly, sinofris, jaw hypoplasia and especial flexion of the fingers on both hands was observed, which

A B

C


Figure 3. A. Female patient diagnosed as OpitzG/B.B.B. syndrome, with hypertelorism, unilateral cleft lip and palate and cranio-facial dimorphism B. Karyotype shows a chromosomal translocation between long arms of chromosomes 3 and 4, 46XX t(3q;4q).

Figure 4. A. Male patient diagnosed as Wolf-Hirshhorn syndrome, with tippical phenotype, facial dysmorphism like "greek helmet": prominent glabela, ocular hypertelorism, epicanthal folds and marked broad-beaked nose and microphtalmia. B. karyotype revealed loss of genetic material at chromosome 4 short arm, A case of probable de novo mutation with deletion of gene WHSC1 and other linked contiguous genes.

karyotype reveals an 18 trisomy (Figure 21 A, B, C and D) and only one male patient with mental retardation, epileptic seizures microcephaly, and hypoplasia was diagnosed as trisomy 22, (47 XY + 22) (Figure 25 A, B and C).

Chromosome deletions 4p-, 5p- and 9q- were also diagnosed. Figure 4 A and B, shows a male patient

diagnosed as Wolf-Hirshhorn syndrome, with typical phenotype, facial dimorphism like "greek helmet": prominent glabella, ocular hypertelorism, epicanthic folds and marked broad-beaked nose and microphtalmia with a loss of genetic material at chromosome 4 short ar. A case of probable de novo mutation with deletion of gene WHSC1 and other linked contiguous genes (Aparicio et

A B

A B


Figure 5. A. Male patient diagnosed as Cri du chat syndrome, with oddly shaped ears. This syndrome is a type of mental retardation, develop slowly mentally and have wide set eyes. B. karyotype revealed loss of genetic material at chromosome 5 short arm.

Figure 6. Female patient diagnosed with none phenotypical malformations nor A. B. cranio-facial dimorphism C. karyotype revealed complete trisomy of chromosome 6.

al., 1997; Aviña and Hernandez, 2008), different clinical features from the male patient diagnosed as Cri du chat syndrome, with oddly shaped ears. This syndrome is a type of mental retardation, develop slowly mentally and have wide set eyes. "Cri du chat" means "cry of the cat" in french, and the condition was so-named because affected babies make high-pitched cries that sound like those of a cat. The patient karyotype revealed loss of genetic material at chromosome 5 short arm (Figure 5 A and B). Karyotype from a male patient revealed a chromosome deletion of the long arm of chromosome 9 (46, XY, del 9q) (Figure 11 A and B).

Other chromosomal aberrations were also observed in this study as inversions and ring alterations; a patient with both deletion and inversion 46, XX, inv (10q)/del (10p) was diagnosed in a patient with juvenile polyposis syndrome, where multiple polyps appear in the gastrointestinal tract. Colonoscopy was performed and hundreds of pedunculated and sessile polyps were observed in the entire colon and were submitted twice to surgical procedures, resected and studied resulting as inflammatory polyps (Figure 13 A, B and C) (Aparicio et al., 2009). Different from both chromosomal 13 and 18 ring aberrations; Figure 15 A, B and C shows a female patient with bilateral cleft lip and palate and cranio-facial dimorphism and hypertelorism characterized by progressive deformity of spine with hemivertebrae and 13 chromosome ring malformation (Aparicio et al., 2000),

A

B

A B

C


Figure 7. Male patient. A. with hypertelorism, sinofris B. small nose, hypoplasia of nasal wings. C. karyotype revealed a chromosomal translocation from short arm of chromosome 6 to long arm of chromosome 9 t (6;9).

different clinical features from a male patient with an 18 ring chromosome aberration with general hypoplasia and hipotonía, ambiguous genitalia, hypertelorism and small hands with especial flexion of the fingers (Figure 22 A, B and C) (Aparicio et al., 1998).

In relation to sexual chromosomes, several phenotypical malformations as diphallia were observed in three patients with normal karyotypes; however other

ambiguous genitalia were observed associated to translocation, chromosomal chimera, polyploidy as XXX and Kllinefelter. Also, monosomy as Turner syndrome. Figure 26 A and B shows a male patient diagnosed with Opitz G/B.B.B. syndrome, hypertelorism and cleft lip and palate, cranio-facial dismorphism. However, the karyotype reveals an X sexual chromosome duplication 46, XXY (Klinefelter syndrome). Male with this syndrome

A B

C


Figure 8. A. Healthy carrier mother. B. of a chromosomal translocation 46XX,ins(10;7) (q21;q23q35) C. however her mentally retarded son. D. revealed a balanced chromosomal translocation from long arm of chromosome 10 t(10q+), giving a rise to a partial trisomy 7.

Figure 9. Male patient. A. with a facial hypoplasia, have narow set eyes and sinofris. B. hipoplasic jaw with restricted motion and limited mouth opening C. karyotype revealed a partial trisomy of chromosome 7, 46XY, 7q+.

A B

C D

A B

C


Figure 10. Female patient A. with a facial hypoplasia and oblicua desviation of both eyes, small mouth B. hipoplasic jaw and facial hypoplasia C. karyotype revealed a partial trisomy of chromosome 7, 46XX, 7q+.

Figure 11. A and B. karyotype from a male patient revealed a chromosome deletion of the long arm of chromosome 9 (46, XY,del 9q-).

A B

C

A

B

Figure 12. A. Healthy carrier father. B. of a chromosomal translocation 46XY,ins(10;9) B. And his son with plagiocephaly and facial hemiatrophy C. wide nose and hipoplasic jaw D. However her physically retarded son D. revealed a balanced chromosomal translocation t(9;10) giving a rise to a partial trisomy 9. are usually sterile and have a higher incidence of speech delay and dyslexia. During puberty, without testosterone treatment, some of them may develop gynecomastia. This patient must be evaluated periodically by endocrinology and pediatric surgery.

Opposite features in female patients, diagnosed as Turner syndrome, with small size and pterigium coli. Her Karyotype revealed only one X chromosome (45XO). Turner syndrome (X instead of XX or XY). In Turner syndrome, female sexual characteristics are present but underdeveloped. People with Turner syndrome often have a short stature, low hairline, abnormal eye features and bone development and a "caved-in" appearance to the chest as this patient (Figure 27 A and B), differently to


Figure 13. A. the patient was diagnosed as juvenile polyposis syndrome where multiple polyps appear in the gastrointestinal tract. Colonoscopy was performed and B. hundreds of pedunculated and sessile polyps were observed in the entire colon and were submitted twice to surgical procedures, resected and studied resulting as inflammatory polyps. In relation to genetics. C. karyotype was performed finding a chromosomal formula; 46,XX,inv(10q)/del (10p). this patient a female with cranio-facial dimorphism, small eyes with hypotelorism, turricefalia and hypoplasia was associated to trisomy of X sexual chromosomes 47, XXX (triple-X syndrome) (Figure 28 A, B and C). XXX females tend to be tall and thin. They have a higher incidence of dyslexia and they are somewhat more likely to have learning difficulties. In Figure 29 A and B a male patient with bilateral cryptorchidism and hypospadias is observed, associated to translocation between chromosomes Y and 7, 46 XY t (7; Y) (Aparicio et al., 2010).

Real dipallia is considered a rare event. However, 3 cases are reported in this study; two months old male patient (Figure 30 A and B), four years old male patient (Figure 31 A and B) and sixteen years old male patient (Figure 32 A and B). The three patients karyotype was normal 46XY (Aparicio et al., 2010). During 19 years a chromosomal chimera (an event were two different cell lines 46,XX/46,XY exist in the same patient) associated to ambiguous genitalia in a new born child was observed (Figure 33 A and B). In relation to this patient, it has been discussed among a multidisciplinary medical group,

A

B

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D

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Figure 14. A. Male patient with bilateral cleft lip and palate and cranio-facial dimorphism B. karyotype revealed a partial trisomy of chromosome 14, (14q24 leads to qter) due to a balance translocation t(11;14) (q25;q24.1).

Figure 15. A. Female patient with bilateral cleft lip and palate and cranio-facial dimorphism and hypertelorism B. characterized by progressive deformity of spine with hemivertebrae. C. karyotype revealed a 13 chromosome ring malformation.

A

B

A B

C


Figure 16. A. Female patient with Patau syndrome with hypoplasic face, bilateral cleft lip and palate and cranio-facial dimorphism, absent or malformed nose. B. especial flexion of the fingers on both hands. C. karyotype revealed a 13 chromosome trisomy.

Figure 17. A. A family conformed by a mother and both son and daughter with none phenotipical malformations. Breast cancer was diagnosed to the mother and mastectomy was performed, with B. chromosome translocation between 13 and 15 chromosomes t(13;15). same as C. the translocation found in her son.

A B

C

A

B C


Figure 18. A. New born female patient with cleft palate B. and displasic ears C. karyotype revealed a balanced chromosomal translocation 21;14 due to a 14 trisomy.

Figure 19. A. Male patient with cranio-facial dimorphism diagnosed as Parry Romber syndrome B. karyotype revealed a duplication of the long arm of chromosome 16 (16q+).

A B

C

A B


Figure 20. A. Female patient with obesity and mentally retarded with B. C. none phenotypical malformations. karyotype revealed a duplication on the hetrocomatic region of chromosome 16 46,XX 16qh+ chromosome 21 (46,XX,16qh+,21PSTK+).

Figure 21. A. Male patient with hirsutism, microcephaly, sinofris and general hypoplasia B. hypoplasia of the jaw C. especial flexion of the fingers on both hands D. Karyotype reveals an 18 trisomy.

A B

C

A B

C

D


Figure 22. A. Male patient with general hypoplasia and hipotonía, ambiguos genital and hypertelorism B. Small hands with especial flexion of the fingers C. karyotype reveal an 18 ring chromosome aberration.

Figure 23. A. B. A 6 years old male patient with Down syndrome and mental retardation, C. karyotype reveals a trisomy 21 (47,XX,+21) caused by a meiotic nondisjunction event.

A B

C

A B

C


Figure 24. A. B. An 8 years old female patient with Down syndrome, mental retardation, and epilepsy. C. karyotype reveals a Robertsonian translocation. The long arm of chromosome 21 is attached to chromosome 14 (46,XX,t(14;21q).

whether the patient must keep its personal sexual identity as a male or female, since half of the sexual chromosomal information is XX and half is XY. It is

important to decide it according to the future sexual behavior, physical function and genital external structure of the patient. A decision must be taken by the

A B

C


Figure 25. A. A 2 months old male patient with mental retardation, epileptic seizures microcephaly, and B. hypoplasia C. karyotype reveals a trisomy 22, 47 XY + 22.

multidisciplinary medical group and the patient´s family (Aparicio et al., 2010). Conclusions Some mutations are neutral and have little or no effect. However, another chromosomal aberration, change the

patient’s life and it has a great role in evolution. Therefore, international associations and institutions as the Vega Institute present data from the manual annotation of the human genome. The annotation shown in this release of Vega is from a data freeze taken from 2008 to 2011 and the gene structures (Table 2).

Abnormal numbers of chromosomes or chromosome sets, aneuploidy, may be lethal or give rise to genetic

A B

C


Figure 26. A. Male patient diagnosed with Opitz G/B.B.B. síndrome, hypertelorism and cleft lip and palate, cranio-facial dimorphism B. karyotype reveals an X sexual chromosome duplication ( Klinefelter syndrome).

Figure 27. A. Female patient with Turner syndrome, small size and pterigium coli B. karyotype reveals an X chromosome (45XO).

Figure 28. A. Female patient with cranio-facial dimorphism, small eyes with hypotelorism B. turricefalia and hypoplasia C. karyotype reveals a trisomy of X sexual chromosomes (47, XXX).

A

B

A B

C

A B

C


Figure 29. A. Two years old male patient with bilateral cryptorchidism and hypospadias B. karyotype reveals a chromosome translocation between chromosomes Y and 7, 46 XY t(7;Y).

Figure 30. A. Two months old male patient with real diphallia. B. karyotype was normal 46XY.

Figure 31. A. Four years old male patient with real diphallia. B. karyotype was normal 46XY.

A B

A B

A B


Figure 32. A. Sixteen years old male patient with real diphallia. B. karyotype was normal 46XY.

Figure 33. A. New born patient with ambiguous genitalia B. Karyotype reveals a chromosomal chimera with two different cell lines 46,XX/46,XY.

A B


Figure 34. 4617 karyotypes were performed from 1992 to 2011, where 1596 patients (34.6%) showed chromosomal alterations.

Table 2. Sequencing (http://www.ncbi.nlm.nih.gov/genome/seq/) of the human genome has provided a great deal of information about each of the chromosomes. This table is compiling statistics for the chromosomes, based on the Sanger Institute's human genome information in the Vertebrate Genome Annotation (VEGA) database. Vega.sanger.ad.uk, 2008-2011.

Chromosome Genes Total bases Sequenced bases (http://pediaview.com/openpedia/Chromosomes)

1 4,220 247,199,719 224,999,719 2 1,491 242,751,149 237,712,649 3 1,550 199,446,827 194,704,827 4 446 191,263,063 187,297,063 5 609 180,837,866 177,702,766 6 2,281 170,896,993 167,273,993 7 2,135 158,821,424 154,952,424 8 1,106 146,274,826 142,612,826 9 1,920 140,442,298 120,312,298 10 1,793 135,374,737 131,624,737 11 379 134,452,384 131,130,853 12 1,430 132,289,534 130,303,534 13 924 114,127,980 95,559,980 14 1,347 106,360,585 88,290,585 15 921 100,338,915 81,341,915 16 909 88,822,254 78,884,754 17 1,672 78,654,742 77,800,220 18 519 76,117,153 74,656,155 19 1,555 63,806,651 55,785,651 20 1,008 62,435,965 59,505,254 21 578 46,944,323 34,171,998 22 1,092 49,528,953 34,893,953

X (sex chromosome) 1,846 154,913,754 151,058,754 Y (sex chromosome) 454 57,741,652 25,121,652

Total 32,185 3,079,843,747 2,857,698,560 disorders (Huret et al., 2000). Some of the main chromosomal alterations in this study can be seen in Table 1 and Figure 35. Genetic counseling was offered

for carrier families (Figures 8 A, B, C, D, 12 A, B, C, D and 17 A, B, C), that carry these chromosome rearrangements. The gain or loss of DNA from

Total normal patients Patients with chromosomomal alterations


Trisomy

Deletion

Inversion

Ring

Duplication

Translocation

Monosomy

Chimera

CHROMOSOMAL ALTERATIONS IN 19 YEARS

H.N.P. (1596 PATIENTS)

9

15

4

2

1

11

1

1553

Figure 35. Chromosomal alterations in 19 years, shows 1596 patients (34.6%) with different aberrations. From these, 1553 (33.6%) were trisomy.

Trisomy

Translocation 14;21

Translocation 21;21

Mosaicism

43 81

MAIN TRISOMY 21

H.N.P. (1511 PATIENTS)

1127

260

Figure 36. From all chromosomal trisomies 1553 (33.6%), It can be seen that 1511 (32.7%) were different kind of trisomy 21.

chromosomes can lead to a variety of genetic disorders as it was found in this study. It might be important if

chromosomal aberrations can be diagnosed early, which will contribute for an early treatment. It is also primordial

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main chromosome aberrations among 4617 chromosomal ......as cementoma gigantiforme (and been...

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