Abstract
Purpose: :
Albinism shows a broad phenotypic spectrum. The phenotype ranges from complete lack of pigmentation in skin, hair, iris and RPE (OCA) to a lack of pigmentation in iris and RPE only (OA). Every possible nuance will occur. The spectrum in part is associated with genetic heterogeneity due to at least five known genes involved in man (TYR, P, TRP, MATP, OA1). Further genes have to be expected since the known five cover only a minor fraction of the patients. In addition mutations in TYR and P are known to present with reduced function of various extend thus causing light phenotypes of many nuances. This study was designed to identify the fraction of patients presenting with albinism of all nuances of expression caused by mutations in TYR, P, and OA1.
Methods: :
125 patients diagnosed with albinism by standard ophthalmological methods were subjected to molecular genetic screening for mutations in TYR, P, and OA1. The set of patients contained index cases of OCA, OA3, OA1, and not further specified OA.
Results: :
Most of the OCA patients showed a light complexion without unambiguous albinotic features of skin and hair. Their diagnosis was frequently done by additional symptoms like macular hypoplasia, nystagmus, and fundus hypopigmentation. Index cases with OA were classified as OA1 when only males were affected in the family and when their mothers were diagnosed with carrier signs. OA3 was assigned to female cases and when X-linked inheritance could be excluded.We could identify compound heterozygous and homozygous mutations in 19 / 72 (26.3%) patients with OCA (15 TYR, 4 P), 16 / 28 (57%) index cases with OA1, 2 / 7 (28,6%) index cases with OA3 + (2 P), and 6 / 12 (50%) index cases with further not specified OA (3 TYR, 3 P). Mutations in the single heterozygous state could be shown in OA (1 TYR + 1 P) and OCA (3 TYR + 13 P). R402Q and P406L were the most prevalent mutations in TYR. V434I and N489D were most frequent in P.
Conclusions: :
OA1 correlated well with mutations in OA1 in males with a family history of OA1. The frequency of female cases of OA/OA3 with mutations in TYR and P was comparable to that observed among OCA cases but TYR mutations were more frequent than in P in OCA. The high frequency of R402Q in TYR among OA cases is in line with its evaluation as a mutation of moderately reduced function. The frequency of patients not correlated with mutations points to the influence of the know 200 genes involved in hair and skin colour.
Keywords: genetics • gene screening • nystagmus