A novel TECTA mutation confirms the recognizable phenotype among autosomal recessive hearing impairment families
A novel TECTA mutation confirms the recognizable phenotype among autosomal recessive hearing impairment families
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DOI：
10.1016/j.ijporl.2007.09.023
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发表时间：
2008-02-01
影响因子：
1.5
通讯作者：
Van Camp, Guy
中科院分区：
文献类型：
--
作者：
Alasti, Fatemeh;Sanati, Mohammad Hossein;Van Camp, Guy
TECTA 基因突变会导致感音神经性非综合征性听力障碍。 TECTA 相关性耳聋可以是常染色体显性遗传（称为 DFNA8/12）或常染色体隐性遗传（称为 DFNB21）。由 TECTA 基因编码的 a-tectorin 蛋白是内耳盖膜的主要成分之一。 TECTA 基因中的六种突变已在常染色体隐性遗传非综合征性听力障碍家族中被报道。在这项研究中，通过对与 TECTA 基因密切相关的两个短串联重复标记进行基因分型，分析了 75 个分离常染色体隐性非综合征性听力障碍的伊朗家庭的 DFNB21 基因座的纯合性。在所研究的 1/75 个家族中发现了与 DFNB21 基因座可能连锁一致的等位基因分离。通过对 TECTA 的所有 23 个编码外显子进行测序，发现外显子 21 中存在 16 bp 缺失 (c.6203-6218del16)，导致移码，与听力损失分离。该家庭的所有 3 名受影响个体在所有频率上都有中度至重度听力损失，这在中频中更为明显。这种新突变以及之前报道的 TECTA 基因中的六种突变正在失活。这些突变的 AR 导致容易识别的中度至重度听力障碍的听力特征，正如该家庭在本研究中所呈现的那样。 TECTA 常染色体隐性遗传非综合征性耳聋表型不同于典型的重度耳聋表型，后者见于大多数分离常染色体隐性非综合征性耳聋的家族。根据可识别的表型，我们建议对具有这种听力表型的家庭进行 TECTA 突变筛查。 (C) 2007 Elsevier Ireland Ltd. AR 保留权利。
Mutations in the TECTA gene result in sensorineural non-syndromic hearing impairment. TECTA-related deafness can be inherited autosomal dominantly (designated as DFNA8/12) or autosomal recessively (as DFNB21). The a-tectorin protein, which is encoded by the TECTA gene, is one of the major components of the tectorial membrane in the inner ear. Six mutations in the TECTA gene have already been reported in families segregating autosomal recessive non-syndromic hearing impairment. In this study, seventy-five Iranian families segregating autosomal recessive non-syndromic hearing impairment were analyzed for homozygosity at the DFNB21 locus by genotyping two short tandem repeat markers closely linked to the TECTA gene. Allelic segregation consistent with possible linkage to the DFNB21 Locus was found in 1/75 families studied. By sequencing all 23 coding exons of TECTA, a 16 bp deletion (c.6203-6218del16) in exon 21, leading to a frameshift, segregating with the hearing loss was found. All 3 affected individuals of this family have moderate-to-severe hearing loss across all frequencies, which is more pronounced in the mid frequencies. This new mutation, as well as the six previously reported mutations in the TECTA gene, is inactivating. AR of these mutations lead to an easily recognized audiometric profile of moderate to severe hearing impairment as presented by the family in this study too. The TECTA autosomal recessive non-syndromic deafness phenotype differs from the typical profound deafness phenotype that is seen in most families segregating autosomal recessive non-syndromic deafness. On the basis of the recognizable phenotype, we recommend mutation screening of TECTA in families with this hearing phenotype. (C) 2007 Elsevier Ireland Ltd. AR rights reserved.