Apparent digenic inheritance of Waardenburg syndrome type 2 (WS2) and autosomal recessive ocular albinism (AROA)
Apparent digenic inheritance of Waardenburg syndrome type 2 (WS2) and autosomal recessive ocular albinism (AROA)
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DOI：
10.1093/hmg/6.5.659
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发表时间：
1997-05-01
影响因子：
3.5
通讯作者：
Asher, JH
中科院分区：
文献类型：
--
作者：
Morell, R;Spritz, RA;Asher, JH
Waardenburg综合征(WS)是一种临床和遗传异质性疾病，占先天耳聋人口的2%，其特征是耳聋伴发色素异常和神经脊组织的各种缺陷，根据临床和遗传学标准，至少可识别四种类型(WS1、WS2、WS3和WS4)。先前描述的两个家系似乎描述了一个新的亚型，其特征是WS2合并眼白化病(OA)，由于MITF基因的突变是导致WS2的一些病例的原因，我们对其中一个WS2-OA家系进行了突变筛查，发现MITF的外显子8有1个碱基缺失。在这个家族中，所有具有OA表型的个体都是TYR402Q纯合子或杂合子，以及MITF中1个碱基缺失的杂合子。这表明WS2-OA的表型可能是转录因子基因(MITF)和其调控基因(TYR)之间的双基因相互作用的结果。
Waardenburg syndrome (WS) is a clinically and genetically heterogeneous disease accounting for >2% of the congenitally deaf population, It is characterized by deafness in association with pigmentary anomalies and various defects of neural crest-derived tissues, At least four types are recognized (WS1, WS2, WS3 and WS4) on the basis of clinical and genetic criteria. Two previously described families seemed to delineate a new subtype characterized by WS2 in conjunction with ocular albinism (OA), Since mutations in the MITF gene are responsible for some instances of WS2, we screened for mutations in one of the WS2-OA families and discovered a 1 bp deletion in exon 8 of MITF. OA previously has been associated with compound heterozygosity for a mutant TYR allele and the TYRR402Q allele, a functionally significant polymorphism that is associated with moderately reduced tyrosinase catalytic activity, In this family, all of the individuals with the OA phenotype are either homozygous or heterozygous for TYRR402Q, and heterozyous for the 1 bp deletion in MITF. This suggests that the WS2-OA phenotype may result from digenic interaction between a gene for a transcription factor (MITF) and a gene that it regulates (TYR).