Mutations in the TMPRSS3 gene are a rare cause of childhood nonsyndromic deafness in Caucasian patients
Mutations in the TMPRSS3 gene are a rare cause of childhood nonsyndromic deafness in Caucasian patients
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DOI：
10.1007/s00109-001-0310-6
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发表时间：
2002-02-01
影响因子：
4.7
通讯作者：
Antonarakis, SE
中科院分区：
文献类型：
--
作者：
Wattenhofer, M;Di Iorio, MV;Antonarakis, SE
先前报道过位于染色体 21q22.3 上的两个非综合征性隐性耳聋基因座：DFNB8 和 DFNB10。最近发现编码跨膜丝氨酸蛋白酶 TMPRSS3 或 ECHOS1 的基因与 DFNB8 和 DFNB10 表型有关。为了确定 TMPRSS3 突变在一般先天性/儿童非综合征性聋人群体中的贡献，我们对来自西班牙的 448 名无关聋人患者进行了 TMPRSS3 基因突变分析。意大利、希腊和澳大利亚没有常见的 35delG GJB2 突变。我们从研究的 896 条染色体中鉴定出两种新的致病性突变，它们导致了 4 个突变等位基因和至少 16 个非致病性序列变体。致病性突变是 1 bp 缺失，导致 TMPRSS3 的 LDLRA 结构域发生移码和氨基酸取代。根据这项研究和另一项研究，我们估计样本中 TMPRSS3 突变的频率为 0.45%，在一般白种人儿童聋哑人群中约为 0.38%。然而，TMPRSS3 仍然是具有大近亲家庭的人群中遗传性耳聋的重要促成因素。
Two loci for nonsyndromic recessive deafness located on chromosome 21q22.3 have previously been reported, DFNB8 and DFNB10. Recently a gene which encodes a transmembrane serine protease, TMPRSS3 or ECHOS1, was found to be responsible for both DFNB8 and DFNB10 phenotypes. To determine the contribution of TMPRSS3 mutations in the general congenital/childhood nonsyndromic deaf population we performed mutation analysis of the TMPRSS3 gene in 448 unrelated deaf patients from Spain. Italy, Greece, and Australia who did not have the common 35delG GJB2 mutation. From the 896 chromosomes studied we identified two novel pathogenic mutations accounting for four mutant alleles and at least 16 nonpathogenic sequence variants. The pathogenic mutations were a 1-bp deletion resulting in a frameshift and an amino acid substitution in the LDLRA domain of TMPRSS3. From this and another study we estimate the frequency of TMPRSS3 mutations in our sample as 0.45%, and approximately 0.38% in the general Caucasian childhood deaf population. However, TMPRSS3 is still an important contributor to genetic deafness in Populations with large consan-guineous families.