de Moraes Vanessa Cristine Sousa, dos Santos Nathalia Zocal Pereira, Ramos Priscila Zonzini, Svidnicki Maria Carolina Costa Melo, Castilho Arthur Menino, Sartorato Edi Lúcia
Center of Molecular Biology and Genetic Engineering (CBMEG), Molecular Biology Laboratory, State University of Campinas - UNICAMP, Campinas, São Paulo, Brazil.
Int J Pediatr Otorhinolaryngol. 2013 Mar;77(3):410-3. doi: 10.1016/j.ijporl.2012.11.042. Epub 2012 Dec 27.
The SLC26A4 gene has been described as the second gene involved in most cases of sensorineural non-syndromic hearing loss, since the first is the GJB2 gene. Recessive mutations in the SLC26A4 gene encoding pendrin, an anion transporter, are responsible for non-syndromic hearing loss associated with an enlarged vestibular aqueduct (EVA) and Pendred syndrome, which causes early hearing loss and affects the thyroid gland. Typically, the hearing loss is profound and prelingual. However, in some individuals, hearing impairment may develop later in childhood and then progress. Over 200 different SLC26A4 mutations have been reported, with each ethnic population having its own distinctive mutant allele series including a few prevalent founder mutations.
Perform the screening of the 20 coding exons of SLC26A4 gene in Brazilian deaf individuals with EVA.
Among the 23 unrelated non-syndromic hearing loss Brazilian patients with EVA, in whom no deafness-causing mutations of the GJB2 gene, the direct sequencing was performed to screen the 20 exons and their flanking regions of the SLC26A4 gene.
The sequencing results revealed 9 cases (39%) carrying 13 different SLC26A4 mutations, including 11 known mutations (279delT, V138F, T193I, IVS8+1G>A, T410M, Q413R, R409H, L445W, IVS15+5G>A, V609G, and R776C) and 2 novel mutation (G149R and P142L).
The SLC26A4 mutations have a high carrying rate in non-syndromic hearing loss Brazilian patients. The identification of a disease-causing mutation can be used to establish a genotypic diagnosis and provide important information to the patients and their families.
SLC26A4基因被认为是大多数感音神经性非综合征性听力损失病例中涉及的第二个基因，第一个是GJB2基因。编码阴离子转运体pendrin的SLC26A4基因中的隐性突变，是与前庭导水管扩大（EVA）相关的非综合征性听力损失以及Pendred综合征的病因，Pendred综合征会导致早期听力损失并影响甲状腺。通常，听力损失严重且发生在语言发育前。然而，在一些个体中，听力障碍可能在儿童期后期出现并随后进展。已报道超过200种不同的SLC26A4突变，每个种族群体都有其独特的突变等位基因系列，包括一些常见的奠基者突变。
对巴西患有EVA的聋人个体进行SLC26A4基因20个编码外显子的筛查。
在23名不相关的患有EVA的巴西非综合征性听力损失患者中，这些患者中未发现GJB2基因的致聋突变，对SLC26A4基因的20个外显子及其侧翼区域进行直接测序以进行筛查。
测序结果显示9例（39%）携带13种不同的SLC26A4突变，包括11种已知突变（279delT、V138F、T193I、IVS8+1G>A、T410M、Q413R、R409H、L445W、IVS15+5G>A、V609G和R776C）和2种新突变（G149R和P142L）。
SLC26A4突变在巴西非综合征性听力损失患者中的携带率很高。致病突变的鉴定可用于建立基因型诊断，并为患者及其家属提供重要信息。
