Alasti Fatemeh, Sanati Mohammad Hossein, Behrouzifard Amir Hossein, Sadeghi Abdorrahim, de Brouwer Arjan P M, Kremer Hannie, Smith Richard J H, Van Camp Guy
Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
Int J Pediatr Otorhinolaryngol. 2008 Feb;72(2):249-55. doi: 10.1016/j.ijporl.2007.09.023. Epub 2007 Nov 19.
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 alpha-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 16bp 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. All 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.
TECTA基因突变会导致感音神经性非综合征性听力障碍。与TECTA相关的耳聋可呈常染色体显性遗传（称为DFNA8/12）或常染色体隐性遗传（称为DFNB21）。TECTA基因编码的α - 耳畸蛋白是内耳盖膜的主要成分之一。在常染色体隐性非综合征性听力障碍的家系中，已经报道了TECTA基因的六个突变。在本研究中，通过对与TECTA基因紧密连锁的两个短串联重复序列标记进行基因分型，分析了75个常染色体隐性非综合征性听力障碍的伊朗家系在DFNB21位点的纯合性。在所研究的75个家系中，在1个家系中发现等位基因分离与DFNB21位点可能存在连锁关系。通过对TECTA基因的所有23个编码外显子进行测序，发现在外显子21中有一个16bp的缺失（c.6203 - 6218del16），导致移码突变，且该突变与听力损失共分离。这个家系的所有3名受影响个体在所有频率上都有中度至重度听力损失，在中频更为明显。这个新突变以及先前报道的TECTA基因的六个突变都是失活突变。所有这些突变也导致了本研究中该家系所呈现的中度至重度听力障碍的易于识别的听力图特征。TECTA常染色体隐性非综合征性耳聋表型不同于大多数常染色体隐性非综合征性耳聋家系中所见的典型重度耳聋表型。基于可识别的表型，我们建议对具有这种听力表型的家系进行TECTA基因突变筛查。
