Mutations of coding regions and splice sites of SLC26A4 cause Pendred syndrome and nonsyndromic recessive hearing loss DFNB4. SLC26A4 encodes pendrin, a transmembrane exchanger of anions and bases. The mutant SLC26A4 phenotype is characterized by inner ear malformations, including an enlarged vestibular aqueduct (EVA), incomplete cochlear partition type II and modiolar hypoplasia, progressive and fluctuating hearing loss, and vestibular dysfunction. A thyroid iodine organification defect can lead to multinodular goiter and distinguishes Pendred syndrome from DFNB4. Pendred syndrome and DFNB4 are each inherited as an autosomal recessive trait caused by biallelic mutations of SLC26A4 (M2). However, there are some EVA patients with only one detectable mutant allele (M1) of SLC26A4. In most European-Caucasian M1 patients, there is a haplotype that consists of 12 variants upstream of SLC26A4, called CEVA (Caucasian EVA), which acts as a pathogenic recessive allele in trans to mutations affecting the coding regions or splice sites of SLC26A4. This combination of an M1 genotype with the CEVA haplotype is associated with a less severe phenotype than the M2 genotype. The phenotype in EVA patients with no mutant alleles of SLC26A4 (M0) has a very low recurrence probability and is likely to be caused by other factors.

SLC26A4编码区和剪接位点的突变导致 Pendred 综合征和非综合征性隐性听力损失 DFNB4。SLC26A4编码 pendrin，一种阴离子和碱基的跨膜交换剂。突变的SLC26A4表型以内耳畸形为特征，包括前庭导水管 (EVA) 扩大、II 型耳蜗分区不完全和耳蜗发育不全、进行性和波动性听力损失以及前庭功能障碍。甲状腺碘组织缺陷可导致多结节性甲状腺肿并将 Pendred 综合征与 DFNB4 区分开来。Pendred 综合征和 DFNB4 均作为常染色体隐性遗传，由SLC26A4的双等位基因突变引起(M2)。然而，有一些 EVA 患者只有一个可检测的SLC26A4突变等位基因 (M1) 。在大多数欧洲-高加索 M1 患者中，有一个单倍型由SLC26A4上游的 12 个变体组成，称为 CEVA（高加索 EVA），它作为一个致病性隐性等位基因反式突变，影响SLC26A4的编码区或剪接位点。M1 基因型与 CEVA 单倍型的这种组合与比 M2 基因型更不严重的表型相关。没有SLC26A4 （M0）突变等位基因的EVA患者的表型复发概率非常低，很可能是由其他因素引起的。