Makishima Tomoko, Madeo Anne C, Brewer Carmen C, Zalewski Christopher K, Butman John A, Sachdev Vandana, Arai Andrew E, Holbrook Brenda M, Rosing Douglas R, Griffith Andrew J
Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville 20850-3320, Maryland, USA.
Am J Med Genet A. 2007 Jul 15;143A(14):1592-8. doi: 10.1002/ajmg.a.31793.
Dominant, truncating mutations of eyes absent 4 (EYA4) on chromosome 6q23 can cause either nonsyndromic hearing loss DFNA10 or hearing loss with dilated cardiomyopathy (DCM). It has been proposed that truncations of the C-terminal Eya domain cause DFNA10 whereas upstream truncations of the N-terminal variable region cause hearing loss with DCM. Here we report an extended family co-segregating autosomal dominant, postlingual-onset, progressive, sensorineural hearing loss (SNHL) with a novel frameshift mutation, 1,490insAA, of EYA4. The 1,490insAA allele is predicted to encode a truncated protein with an intact N-terminal variable region, but lacking the entire C-terminal Eya domain. Clinical studies including electrocardiography, echocardiography, and magnetic resonance imaging (MRI) of the heart in nine affected family members revealed no DCM or associated abnormalities and confirmed their nonsyndromic phenotype. These are the first definitive cardiac evaluations of DFNA10 hearing loss to support a correlation of EYA4 mutation position with the presence or absence of DCM. These results will facilitate the counseling of patients with these phenotypes and EYA4 mutations.
6号染色体q23区域上眼睛缺失4（EYA4）基因的显性截短突变可导致非综合征性听力损失DFNA10或伴有扩张型心肌病（DCM）的听力损失。有人提出，C末端Eya结构域的截短会导致DFNA10，而N末端可变区的上游截短会导致伴有DCM的听力损失。在此，我们报告了一个大家庭，其共分离常染色体显性、语言后起病、进行性、感音神经性听力损失（SNHL），并伴有EYA4基因的一个新的移码突变1490insAA。1490insAA等位基因预计编码一种截短蛋白，其N末端可变区完整，但缺少整个C末端Eya结构域。对9名受影响家庭成员进行的包括心电图、超声心动图和心脏磁共振成像（MRI）在内的临床研究显示，没有DCM或相关异常，证实了他们的非综合征表型。这些是对DFNA10听力损失的首次明确心脏评估，以支持EYA4突变位置与DCM存在与否之间的相关性。这些结果将有助于为具有这些表型和EYA4突变的患者提供咨询。
