AlAbdi Lama, Alshammari Muneera, Helaby Rana, Khan Arif O, Alkuraya Fowzan S
Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.
Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Hum Genet. 2023 Jan;142(1):139-144. doi: 10.1007/s00439-022-02489-y. Epub 2022 Sep 27.
Oculocutaneous albinism (OCA) is a group of Mendelian disorders characterized by hypopigmentation of skin, hair and pigmented ocular structures. While much of the genetic heterogeneity of OCA has been resolved, many patients still lack a molecular diagnosis following exome sequencing. Here, we report a consanguineous family in which the index patient presented with OCA and Hirschsprung disease but tested negative for known genetic causes of OCA. Instead, he was found to have a homozygous presumptive loss of function variant in PMEL. PMEL encodes a scaffolding protein that is essential for the normal maturation of melanosomes and normal deposition of the melanin pigment therein. Numerous PMEL vertebrate ortholog mutants have been reported and all were characterized by conspicuous pigmentary abnormalities. We suggest that the patient we report is the first human equivalent of PMEL loss of function.
眼皮肤白化病（OCA）是一组孟德尔疾病，其特征为皮肤、毛发和色素性眼结构色素减退。虽然OCA的许多遗传异质性问题已得到解决，但许多患者在外显子组测序后仍缺乏分子诊断结果。在此，我们报告一个近亲家庭，其中先证者患有OCA和先天性巨结肠，但针对已知的OCA遗传病因检测呈阴性。相反，发现他在PMEL基因中有一个纯合的推定功能丧失变异。PMEL编码一种支架蛋白，该蛋白对于黑素小体的正常成熟以及黑色素在其中的正常沉积至关重要。已报道了许多PMEL脊椎动物直系同源突变体，所有这些突变体均具有明显的色素异常特征。我们认为，我们报告的该患者是首例人类PMEL功能丧失的病例。
