Prenatal Genotyping of Four Common Oculocutaneous Albinism Genes in 51 Chinese Families

Oculocutaneous albinism（OCA） is an autosomal recessive disorder characterized by hypopigmentation in eyes,hair and skin,accompanied with vision loss.Currently,six genes have been identified as causative genes for non-syndromic OCA（OCA-1w4,6,7）,and ten genes for syndromic OCA（HPS-1e9,CHS-1）.Genetic counseling of 51 Chinese OCA families（39 OCA-1 with mutations in the TYR gene,6 OCA-2 with mutations in the OCA2 gene,4 OCA-4 with mutations in the SLC45A2 gene,1 HPS-1（Hermanskye Pudlak syndrome-1） with mutation in the HPS1 gene,and 1 mixed OCA-1 and OCA-4） led us to perform the prenatal genetic testing of OCA using amniotic fluid cells through the implementation of our optimized strategy.In our cohort,eleven previously unidentified alleles（PUAs）（5 in TYR,2 in OCA2,and 4 in SLC45A2） were found.Three missense PUAs（p.C112 R,p.H363 R and p.G379 V of TYR） and one in-frame deletional PUA（p.S222 del of SLC24A5） led to fetuses with OCA when co-inherited with other disease causative alleles.Three PUAs（p.P152 H and p.W272 X of TYR,p.A486 T of SLC24A5） identified in the OCA probands did not co-transmit with known pathological alleles and thus gave rise to unaffected fetuses.Four PUAs（p.Q83 X and p.A658 T of TYR,p.G161 R and p.G366 R of SLC24A5） did not transmit to the unaffected fetuses.In addition,the in vitro transfection assays showed that the p.S192 Y variant of TYR produced less pigment compared to the wild-type allele.A fetus with a digenic carrier of OCA-1 and OCA-4 was unaffected.In combination with functional assays,the family inheritance pattern is useful for the evaluation of pathogenicity of PUAs and genetic counseling of OCA.

Application of multiplex ligation-dependent probe amplification in the genetic testing of oculocutaneous albinism

To the Editor: Oculocutaneous albinism (OCA) is an autosomal recessive disorder caused by a group of mutations related to the regulation of melanin synthesis and melanosome biogenesis. The prevalence of OCA worldwide is approximately 1 in 17,000.[1] Other than symptomatic treatment, there is no effective treatment for albinism. Due to the variability in clinical phenotypes, it is difficult to classify sub-types simply by clinical features;therefore, molecular and genetic analyses are the most reliable methods for confirming diagnosis, carrier screening, and pre-natal diagnosis.

Sporadic Porphyria Cutanea Tarda Induced by Alcohol Abuse

To the Editor： A 50-year-old man presented with recurrent episodes of bullae, erosions, and crust on sun-exposed areas for 1 year. Lesions healed with scarring and hyperpigmentation. The skin lesions were aggravated after sun exposure. The patient had a 30-year alcohol abuse （100-200 ml/day） history. Family heredity history was unremarkable. Physical examination revealed multiple erosions with erythema, hyperpigmentation, bullae, and crusting on his lace, neck, and dorsum of the hands [Figure 1a].