Intrafamilial variability of the deafness and Goiter phenotype in Pendred syndrome caused by a T416P mutation in the SLC26A4 gene
Intrafamilial variability of the deafness and Goiter phenotype in Pendred syndrome caused by a T416P mutation in the SLC26A4 gene
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DOI：
10.1210/jc.2004-1013
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发表时间：
2004-11-01
影响因子：
5.8
通讯作者：
Pohlenz, J
中科院分区：
文献类型：
--
作者：
Napiontek, U;Borck, G;Pohlenz, J
Pendred综合征(PS)是综合征性耳聋最常见的原因，占所有常染色体隐性遗传性耳聋病例的5%以上。其特点是双侧感音神经性耳聋和甲状腺肿伴或不伴甲状腺功能减退。SLC26A4基因突变导致典型的PS和与前庭导水管扩大相关的耳聋。为了研究PS的可能的基因型-表型相关性，我们对三个由常见的纯合SLC26A4突变T416P引起的典型PS的成年德国同胞进行了详细的临床和遗传学研究。23年的听力学长期随访显示，T416P突变与三个兄弟姐妹中的每一个都有不同类型的听力损失有关：中度到重度进行性耳聋，重度非进行性耳聋，以及较轻但进展较快的形式。我们发现这些表型差异既不是由不同程度的内耳畸形引起的，也不是由GJB2/连接蛋白26基因的序列变异引起的。由于甲状腺表型在家族内也有很大的差异，甲状腺大小从正常到大的甲状腺肿大需要切除甲状腺，本研究得出结论，其他环境和/或遗传因素也对PS表型有影响。
Pendred syndrome (PS) is the most common cause of syndromic deafness, accounting for more than 5% of all autosomal-recessive hearing loss cases. It is characterized by bilateral sensorineural hearing loss and by goiter with or without hypothyroidism. Mutations in the SLC26A4 gene cause both classical PS and deafness associated with an enlarged vestibular aqueduct without goiter.To investigate a possible genotype-phenotype correlation in PS, we performed a detailed clinical and genetic study in three adult German sibs with typical PS caused by a common homozygous SLC26A4 mutation, T416P. An audiological long-term follow-up of 23 yr showed that the mutation T416P is associated with a distinct type of hearing loss in each of the three sibs: moderate-to-profound progressive deafness, profound nonprogressive deafness, and a milder but more rapidly progressing form. We show that these phenotypic differences are not caused by either different degrees of inner ear malformations or sequence variations in the GJB2/connexin 26 gene.Because the thyroid phenotype was also highly variable within the family, with thyroid sizes ranging from normal to large goiters requiring thyroidectomy, this study leads to the conclusion that other environmental and/or genetic factors have an impact on the PS phenotype.