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/dispomim.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