XLMR Database

D.A. Cabezas,1* J.F. Arena,1,2 R.E. Stevenson,3 C. Schwartz,3 S. Goldberg,1 A. Morales,1 andH.A. Lubs1,4

1University of Miami School of Medicine, Miami, Florida2Marilia Medical School, Sao Paulo, Brazil3JC Self Research Institute, Greenwood, South Carolina4Department of Medical Genetics, University of Tromso, Tromso, Norway

The computer database on X-linked mentalretardation (XLMR) disorders developed byArena and Lubs in 1991 has now been up-dated to include all currently known XLMRdisorders and nonspecific (MRX) families.Currently, it includes 123 syndromes, 59nonspecific XLMR families, and 60 familiesfrom the Miami/Greenwood study. The olderclinical reports have been reviewed and re-vised. The search mechanism has also beenrevised and now includes 740 individual“keywords.” Each of these keywords recog-nizes several of clinical descriptive terms,as used in published literature reports.Searches can be made according to anyclinical finding or combination of findings.For each disorder, the database presents agraphic display that contains a revised andmore complete set of clinical findings, refer-ences, keywords, map localization, molecu-lar information, access to pictures, andOMIM number. Am. J. Med. Genet. 85:202–205, 1999. © 1999 Wiley-Liss, Inc.

KEY WORDS: X-linked; mental retardation;database

INTRODUCTION

There has been a significant increase in the numberof X-linked mental retardation (XLMR) disorders sincethe prior publication in 1991 describing the presentcomputerized approach to XLMR syndromes [Arenaand Lubs, 1991]. These newly described disorders havebeen added to the database and include the syndromesand families with nonspecific XLMR listed in the mostrecent updates [Lubs et al., 1998]. New and updated

features have been included in the program. Thesearch mode has been updated, increasing the numberof words that can be searched to approximately 740different terms. These keywords were designed to rec-ognize the several medical terms that are used by cli-nicians when describing a specific finding. The datacan be sorted by clinical group (such as all syndromes

Contract grant sponsor: NICHD; Contract grant number: R01HD26202-07.

*Correspondence to: D.A. Cabezas, M.D., Ph.D., Mailing Centerfor Child Development (D-820), P.O. Box 016820, Miami, FL33101. E-mail: jarena@mednet.med.miami.edu

Received 22 August 1997; Accepted 16 November 1998

Fig. 1. Display of data for Coffin-Lowry syndrome.

Fig. 2. Display of the “Make Dx” (Make Diagnosis) screen.

American Journal of Medical Genetics 85:202–205 (1999)

© 1999 Wiley-Liss, Inc.

TABLE I. Detail of Search Results Based on Single Keywords

Ref/OMIM no. Keyword/disorders Localization

Short stature 39K8000K8020 Xp11.21K8100 Xq28K8110 Xp11.2–p21K8125K8185K8240 Xq13–q21.3K8250 Xp11.2

305400 Aarskog* Xp11.22300800 Albright hereditary ost.301040 Alpha thalassemia atr-x Xq13.3309530 Atkin-Flaitz301900 Borjeson Xq26–q27301950 Branchial arch

Carpenter Xp11.3–q24309620 Christian Xq27–q28309490 Chudley

Chanchetti305450 FG

Hamel302000 Hered. bullous dyst. Xq26–q28309540 MRX02 Xp22.1–p22.3

MRX06-Kondo Xq27MRX10-Kerr Xp11.4–p21.3MRX11-Kerr Xp11.22–p21.3MRX12-Kerr Xp21.3-q21.1

311300 Otopalato-digital Xq27–q28Porteous Xp11.4–q13

300055 PPM-X Xq28309500 Renpenning Xp21.1–q12314320 Say-Meyer309580 Smith-Fineman-Myers

Stocco dos SantosStoll

309470 Sutherland Xp21.1–q22ThodeTranebjaerg III gynecom

309585 VasquezYoung-Hughes

Early death: 14K8030K8210 Xq28K8300 Xq28K8745

312890 Baar-Gabriel309660 Bergia300067 Berry-Krevis-Israel Xq22–q23

Bertini308830 Cantu

Gustavsson Xq26Holmes-Gang

304340 Pettigrew Xq26–q27.1301790 Schmidley312870 Simpson-Golabi-Behmel* Xq26.1Obesity: 12

K8185300800 Albright hereditary ost309530 Atkin-Flaitz301900 Borjeson Xq26–q27309490 Chudley

Clark-Baraitser300047 MRX20-Lazzarini Xq21.3

MRX35-GU Xq22–q26312870 Simpson-Golabi-Behmel* Xq26.1309585 Vasquez309585 Wilson M Xp21.1–q22

Young-HughesLarge Testes: 11

K8010 Xq12–q21K8025 Xp11–q21K8120K8185

TABLE I. (Continued)

Ref/OMIM no. Keyword/disorders Localization

309530 Atkin-FlaitzClark-Baraitser

309550 Fragilx Xq27.3309540 MRX02 Xp22.1–p22.3300055 PPM-X Xq28

TariverdianTranebjaerg II (ataxia)

Hypertelorism: 16K8020 Xp1 1.21K8185K8210 Xq28K8250 Xp11.2

305400 Aarskog* Xp11.22309530 Atkin-Flaitz303600 Coffin-Lowry* Xp22.2–p22.1305450 FG300000 Opitz-G, Xp22311300 Otopalato-digital Xq27–q28309610 Prieto Xp21.1–p11.22312870 Simpson-Golabi* Xq26.1313420 Spondylometaphyseal

Stoll309480 Tranebjaerg I311450 W syndromeMacrocephaly: 20

K8010 Xq12–q21K8015 Xq28K8100 Xq28K8145 Xp21.2–p22K8185

309530 Atkin-FlaitzClark-Baraitser

305450 FG309550 Fragile X* Xq27.3309540 MRX02-Proops/Arvelier/Hu Xp22.1–p22.3

MRX35-GU Xq22–q26MRX36-Claes Xq21.2–p22.1MRX38-Schutz Xp21.1–p22.13

309610 Prieto Xp21.1–p11.22312870 Simpson–Golabi-Behmel* Xq26.1309583 Snyder-Robinson Xp22.3–p21.3

Tariverdian311510 Waisman-Laxova Xq27.3–q28309585 Wilson M Xp21.1–q22307000 X-Linked synd. hydroceph Xq21–q22Large ears: 14

K8005 Xq13–q12K8055K8185

309530 Atkin-Flaitz301900 Borjeson Xq26–q27

Clark-BaraitserMRX03-Gedeon Xq28MRX10-Kerr Xp11.4–p21.3MRX12-Kerr Xp11.2–p21.3MRX12-Kerr Xp21.3–q21.1MRX13-Kerr Xp22.3–q21.2MRX28-Holinski-Feder Xq28MRX37-Bar David Xp22.31–p22.32

309480 Tranebjaerg IContractures: 13

K8005 Xq13–q12K8075− Xq11–q22K809K8225 Xq13–q21

309600 Allan-Herndon-Dudley Xp11.4–q21.3312890 Baar-Gabriel312920 Goldblatt Xq13–q21.1

MRX28-Holinski-Feder Xq28304340 Pettigrew Xq26–q27.1300004 Proud312840 Schimke313420 Spondylometaphyseal314580 Weacker-Wolff Xq13–q21

*K8000 numbers refer to families in the Miami/Greenwood study.

XLMR Database 203

or nonspecific (MRX) families), clinical features, syn-drome name and map localization. Maps of the bandlocalization can be drawn by either syndrome or key-word. The references and pictures have also been up-dated. Each condition has been assigned an individualcard (Fig. 1) that contains information and allows ac-cess to the multiple features of the program.

DESCRIPTION OF SYSTEM

A Power Macintosh® 9500/150 with 47 MB of activememory and a 2.0 gigabyte storage memory hard driveis currently being used together with a flatbed scannerfor picture input. The system is complemented withsoftware that includes Hypercard® version 2.3, Photo-shop® 4.0, and Microsoft® Office. Publications havebeen obtained from diverse sources that include OMIM[1995], Medline, and literature publications, and theyhave been kept in files for reference. The clinical infor-mation from publications is entered as keywords thatare recognized by the search engine program. Thesekeywords have been organized in both anatomical andorgan-system fashion, as shown in Figure 2. By point-ing the computer cursor toward the upper extremities,for example, a list of keywords will be displayed, whichcan be highlighted and placed into the “New Case” boxautomatically. The search mode is activated throughthe “Make Diagnosis” button (Fig. 2).

RESULTS

Examples of several types of searches are presentedin Tables I to III. Detailed results of a number of singlekeyword searches (short stature, early death, smalltestes, hypertelorism, macrocephaly, contractures, andobesity) are presented in Table I. These findings aresummarized in Table III. An example of a search usingthe “Make Diagnosis” button on the screen shown inFigure 2 using three keywords (short stature, obesity,and hypertelorism) is shown in Table III. This ordersthe search results by the total number of keywordsfound in each disorder. Single keyword “hits” are notshown in this example. It is also possible to create alocalization map individually by keywords, as dis-played in Figure 3, or by syndrome only.

DISCUSSION

The XLMR computer database is presented as a re-source that has been developed to retrieve clinical, ge-netic, and bibliographical information for the varioussyndromes. It also offers diagnostic suggestions by pro-viding correlations between keywords and syndromes.The capability of presenting high-resolution images ofaffected family members allows a comparison of clini-cal features and descriptions beyond what is presentedin a written format. Photographs from several syn-dromes with findings in common, for example, can bedisplayed on the same screen and compared. Theknown map localizations of syndromes can be clusteredor examined individually. Thus, with this feature, acomparison of chromosomal localizations can be pre-sented at the band level of resolution. Limiting mark-ers are being entered into the system to assist in com-paring overlapping localizations.

Several types of searches are available. A search on asingle keyword will reveal a wide variety of informa-tion. Short stature, for example, was described in atotal of 39 disorders of which 26 were described syn-dromes, five were nonspecific (MRX), and eight werefamilies with K8000 numbers in the Miami/Greenwoodstudy (Table II). Out of the 26 described syndromesfound, 16 have been mapped and two have had therespective gene cloned (Table II). Alternatively, a col-lective chromosome map of the localizations of syn-dromes with short stature can be displayed (Fig. 3).Map localizations can also be drawn by regions in orderto look for clusters and regions where a specific combi-nation of clinical findings occurs.

The differential diagnosis between known syn-dromes and clinical findings of unknown etiology canalso be searched. An example of a diagnostic search onshort stature, obesity, and hypertelorism is shown inTable III. One syndrome and family K8185 have allthree clinical findings and several others that have twoin different combinations. This approach not only en-ables relatively rare disorders to be included in thesearch but also allows a clinician to reconsider theclinical findings in a patient or a family and to reex-amine them for additional findings that may have beenmissed on an initial examination.

The XLMR database is also intended as a source of

TABLE II. Summary Table for Single Keyword Search ResultsBased on 123 XLMR Syndromes

Keyword search Disorders MRX Total Localization Cloned

Short stature 26 5 31 16 2Early death 10 0 10 4 1Obesity 9 2 11 5 0Large testes 6 1 7 3 1Hypertelorism 12 0 12 5 3Macrocephaly 11 4 15 11 3Large ears 4 7 11 8 0Contractures 8 1 9 5 0

TABLE III. “Make Diagnosis” Results Based on Short Stature,Obesity, and Hypertelorism

Syndrome

No.of

signs Clinical findings

Atkin-Flaitz 3 Short stature, obesity,hypertelorism

K8185 3 Short stature, obesity,hypertelorism

Young-Hughes 2 Short stature, obesityVasquez 2 Short stature, obesityStoll 2 Short stature, obesitySimpson-Golabi-Behemel 2 Obesity, hypertelorismOtopalato-Digital 2 Short stature, hypertelorismFG 2 Short stature, hypertelorismChudley 2 Short stature, obesityBorjeson 2 Short stature, obesityAlbright hereditary

osteodystrophy 2 Short stature, obesityAarskog 2 Short stature, hypertelorism8250 (Miami/Greenwood) 2 Short stature, hypertelorism8020 (Miami/Greenwood) 2 Short stature, hypertelorism

204 Cabezas et al.

information and a valuable tool for planning, research,and preparation of manuscripts. It can be expandedand updated constantly through the contribution of re-searchers involved in XLMR investigation.

ACKNOWLEDGMENT

Research supported by NICHD R01 HD26202-07.

REFERENCES

Arena JF, Lubs HA. 1991. Computerized approach to X-linked mentalretardation syndromes. Am J Med Genet. 38:190–199.

Lubs HA, Chiurazzi P, Arena JF, Tranebjaerg L, Neri G. 1998. XLMRgenes: update 1998. Am J Med Genet. 83:237–247.

Online Mendelian Inheritance in Man (OMIM). 1995. The Human GenomeDatabase Project. Baltimore: Johns Hopkins University. (World WideWeb).

Fig. 3. Band locations for disorders with short stature, obesity, and hypertelorism.

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