Background: Oculocutaneous albinism type1 (OCA1) is characterized by the absence of melanin pigmentation. The mutation on TYR gene makes OCA1 as an autosomal recessive genetic disorder. In this study, we delineated the genetic analysis of an Iranian family with four members affected with OCA1.
Methods: Clinical exams and paraclinical test were performed for all patients of the case family, also proband, her husband, and her parents. Pedigree chart was drawn too. We extracted the genomic DNA from the leukocytes of seven members of the family. Haplotype analysis at the TYR locus was done and informative microsatellite markers were employed. In order to amplify the entire coding region of the TYR gene, for bidirectional direct sequencing mutation analysis, eight sets of primers were used.
Results: Our patients were diagnosed as affected with Oculocutaneous albinism type1a. Analysis of pedigree pattern showed an autosomal recessive inheritance. Analysis with different markers in chromosomes 5, 6, 9, 11 and 15 showed that cause of albinism in our case family was on chromosome 11 (D11S1887 marker was informative).
Conclusions: The results offered a more developed method of diagnosis for OCA1 carrier identification and genetic counseling for OCA1 affected families as well; also submit a sample of mutation involved with oculocutaneous albinism in Iran. Genetic analysis is necessary for determining the type of albinism in an individual patient.
Keywords: Chromosomes, 11 / Gene, OCA1A /Albinism
Albinism is a heterogeneous group of nonprogressive genetic disorders characterized by complete or partial lack of melanin production in the skin, hair, and/or eyes (1).
Reduction in visual acuity due to the Absence of melanin may occur in some patient (2).
"Oculocutaneous albinism has a wide spectrum; OCA1A is the most severe type with complete melanin reduction and OCA1B, OCA2, OCA3 and OCA4 are the milder types. Although the clinical phenotype of different types of OCA is not always distinguishable, "because of mutations in different genes, making molecular diagnosis is a useful tool and essential for genetic counseling" (2).
"About 1 in 70 people carry a gene for OCA. OCA1 (MIM 203100) is caused by mutations in the tyrosinase gene (TYR, MIM 606933) on chromosome 11q14.3. The gene consists of 5 exons spanning about 65 kb of genomic DNA and encoding a protein of 529 amino acids. TYR (EC 188.8.131.52) is a copper-containing enzyme catalysing the first two steps in the melanin biosynthesis pathway, converting tyrosine to L-dihydroxy- phenylalanine (DOPA) and subsequently to DOPAquinone" (2).
There are two subtype of OCA1; OCA1A and OCA1B. OCA1 is caused by a mutation with complete lack of tyrosinase activity while mutations rendering some enzyme activity result in OCA1B, therefore some melanin pigments are accumulated over time (3).
"Mutations in the OCA2 gene (formerly known as the P-gene) (MIM 203200) cause the OCA2 phenotype (MIM 203200). OCA3 (MIM 203290) is caused by mutations in tyrosinase-related protein 1 (TYRP1, MIM 115501, 9p23)" (2).
"Mutations in the membrane-associated transporter protein gene (MATP, also known as SLC45A2, MIM 606202) cause OCA4 (MIM 606574)" (4).
Initially there was a report in 1989 for mutation in TYR gene (5); almost 200 mutations in TYR are known so far (6).
Our findings will indicate the molecular diagnosis of OCA1 and will present mutation in an ethnic group, in another word, will submit the type of mutation presented in an Iranian family.
Nine members from an Iranian family including a young woman III-9 (normal appearance proband), her parents (II-3 and II-4), her four affected sibs (III-12 to III-15), her husband (III- 8), and her normal sister in law (III-11) actively involved with the present research work. They took part in our interview about their family history and let us to draw the pedigree chart, clinical examinations. …