Phenotypic diversity and genetic complexity ofPAX3-related Waardenburg syndrome
Phenotypic diversity and genetic complexity ofPAX3-related Waardenburg syndrome
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DOI：
10.1002/ajmg.a.61893
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发表时间：
2020-09-29
影响因子：
2
通讯作者：
Shukla, Anju
中科院分区：
文献类型：
--
作者：
Somashekar, Puneeth H.;Upadhyai, Priyanka;Shukla, Anju
Waardenburg综合征亚型1和3是由PAX 3的致病性变体引起的。我们调查了来自4个临床诊断为Waardenburg综合征1/3型的不相关家族的12名个体。在PAX 3中鉴定的新致病性变异包括单核苷酸变异（c.166C>T、c.829C>T）、2个碱基对缺失（c.366_367delAA）和多外显子缺失。对PAX 3中两个新的变异体c.166C>T和c.829C>T以及一个先前报道的变异体c.256A>T进行了核定位和激活MITF启动子的能力的评价。在其中一个受影响的个体中观察到Waardenburg综合征的两种亚型与PAX 3和EDNRB的致病性变体共存。在一个个体中发现了Waardenburg综合征3型和常染色体隐性耳聋1A的多重遗传诊断。我们还回顾了文献报道的PAX 3相关Waardenburg综合征患者的表型和基因组谱。
Waardenburg syndrome subtypes 1 and 3 are caused by pathogenic variants inPAX3. We investigated 12 individuals from four unrelated families clinically diagnosed with Waardenburg syndrome type 1/3. Novel pathogenic variants identified inPAX3included single nucleotide variants (c.166C>T, c.829C>T), a 2-base pair deletion (c.366_367delAA) and a multi-exonic deletion. Two novel variants, c.166C>T and c.829C>T and a previously reported variant, c.256A>T inPAX3were evaluated for their nuclear localization and ability to activateMITFpromoter. The coexistence of two subtypes of Waardenburg syndrome with pathogenic variants inPAX3andEDNRBwas seen in one of the affected individuals. Multiple genetic diagnoses of Waardenburg syndrome type 3 and autosomal recessive deafness 1A was identified in an individual. We also review the phenotypic and genomic spectrum of individuals withPAX3-related Waardenburg syndrome reported in the literature.