oculocutaneous albinism type 1a

Oculocutaneous albinism type 1A

Adrienne Bonvini

What is it? It is an autosomal recessive disorder

characterized by an absence of pigment in the eyes, hair, and skin.

This specific type is characterized by complete lack of tyrosinase activity because an inactive form of the enzyme is produced.

Occurs at a rate of 1/40,000 people

Clinical Features Reduced synthesis

of melanin in the skin, hair, and eyes.

Translucent irises Vision usually in

the range of 20/100 to 20/400

Molecular Genetics OCA1A is caused by mutations of the TYR gene that

produce a inactive form of the tyrosinase enzyme. Parents of an affected child are considered to be

obligate heterozygotes, each carrying a single copy of the disease-causing mutation in the TYR gene.

The gene is located on chromosome 11, at 11q14 – q21

The lack of this enzyme blocks the first step of the melanin biosynthetic pathway, and no melanin is formed in the appropriate melanocytes.

Molecular genetic testing There is evidence of undetected

mutations that may be responsible for OCA1. This evidence is from people with the OCA1A pheotype with only a single identifiable mutation, who are most likely compound heterozygotes with a second mutation that has yet to be identified.

Mutations of the TYR gene Missense subsitutions in the tyrosinase gene

alters codons 355 (thr to lys) and codon 365 (asp to asn). These mutations cause the tyrosinase activity to be disrupted, causing the lack of pigmentation seen in albinism. Both of these mutations occur in the copper binding

region of the enzyme.

Visualization of mutations thr to lys

asp to asn

An example of a tyrosinase

Bibliography http://www.rcsb.org/pdb/explore/explore

.do?structureId=1WX2 http://www.ncbi.nlm.nih.gov/entrez/disp

omim.cgi?id=606933&a=606933_AllelicVariant0003

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=full_report&list_uids=7299

http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=203100