Lim Lynne H Y, Bradshaw John K, Guo Yingshi, Pilipenko Valentina, Madden Colm, Ingala David, Keddache Mehdi, Choo Daniel I, Wenstrup Richard, Greinwald John H
Center for Hearing and Deafness Research, Cincinnati, Ohio, USA.
Arch Otolaryngol Head Neck Surg. 2003 Aug;129(8):836-40. doi: 10.1001/archotol.129.8.836.
To determine the genotypic and phenotypic correlations of hearing impairment (HI) in a midwestern US population related to autosomal recessive nonsyndromic hearing loss locus 1 (DFNB1).
A retrospective review.
Tertiary care children's hospital.
A total of 160 consecutive children diagnosed with idiopathic sensorineural hearing loss.
GJB2 genotype and audiometric phenotype.
The prevalence of subjects with HI having biallelic GJB2-related mutations was 15.3% (24/157). Of these 24 patients, 9 (38%) were homozygous 35delG, 6 (25%) had other biallelic nonsense mutations, and 9 (38%) had a missense mutation of at least 1 allele. The allelic prevalence of 35delG was 8.6% (27/314) in the study population and 48% (23/48) in the DFNB1 group. The M34T allele mutation was next most prevalent at 2.2% (7/314) in the study population and 10% (5/48) in the DFNB1 group. Severe to profound HI occurred in 59% of DFNB1 subjects. Genotypes with biallelic nonsense mutations had a high risk of severe to profound HI (88%). DFNB1-related HI was usually bilateral, symmetric, nonprogressive, and had flat audiograms. However, asymmetric HI (22%), sloping audiograms (26%), and even borderline-normal hearing in 1 ear was observed, and these were associated with the presence of at least 1 missense mutation. Two novel mutations, K15T and L90V, were identified. A subject presenting to our clinic with severe to profound HI had a 40% risk of biallelic GJB2 mutation.
Our population represents a consecutively enrolled clinic population with sensorineural hearing loss. In our DFNB1-related HI cohort, the 35delG mutation and severe to profound HI rates were lower than previously reported. Our missense mutation and M34T allelic prevalence rates were higher than expected and were associated with a less severe hearing loss. The presence of biallelic nonsense mutations was associated with severe to profound hearing loss in nearly 90% of cases. Mild asymmetric HI and sloping audiograms were more often associated with missense mutations.
确定美国中西部人群中与常染色体隐性非综合征性听力损失基因座1（DFNB1）相关的听力障碍（HI）的基因型和表型相关性。
回顾性研究。
三级护理儿童医院。
共160例连续诊断为特发性感音神经性听力损失的儿童。
GJB2基因型和听力表型。
HI患者中双等位基因GJB2相关突变的患病率为15.3%（24/157）。在这24例患者中，9例（38%）为纯合子35delG，6例（25%）有其他双等位基因无义突变，9例（38%）至少有1个等位基因存在错义突变。研究人群中35delG的等位基因患病率为8.6%（27/314），DFNB1组为48%（23/48）。M34T等位基因突变在研究人群中其次常见，为2.2%（7/314），DFNB1组为10%（5/48）。59%的DFNB1受试者发生重度至极重度HI。双等位基因无义突变的基因型发生重度至极重度HI的风险较高（88%）。与DFNB1相关的HI通常为双侧、对称、非进行性，听力图平坦。然而，观察到不对称HI（22%）、听力图呈斜坡状（26%），甚至1只耳朵听力接近正常，这些与至少存在1个错义突变有关。鉴定出两个新突变，K15T和L90V。在我们诊所就诊的重度至极重度HI患者中，双等位基因GJB2突变的风险为40%。
我们的研究人群代表了连续入组的感音神经性听力损失门诊人群。在我们与DFNB1相关的HI队列中，35delG突变和重度至极重度HI发生率低于先前报道。我们错义突变和M34T等位基因患病率高于预期，且与较轻的听力损失相关。双等位基因无义突变的存在在近90%的病例中与重度至极重度听力损失相关。轻度不对称HI和听力图呈斜坡状更常与错义突变相关。
