Schimmenti Lisa A, Martinez Ariadna, Telatar Milhan, Lai Chih-Hung, Shapiro Nina, Fox Michelle, Warman Berta, McCarra Matthew, Crandall Barbara, Sininger Yvonne, Grody Wayne W, Palmer Christina G S
Department of Pediatrics, Institute of Human Genetics, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
Genet Med. 2008 Jul;10(7):517-24. doi: 10.1097/gim.0b013e31817708fa.
Previous studies of connexin-related hearing loss have typically reported on mixed age groups or adults. To further address epidemiology and natural history of connexin-related hearing loss, we conducted a longitudinal study in an ethnically diverse cohort of infants and toddlers under 3 years of age. Our study compares infants with and without connexin-related hearing loss to examine differences in the prevalence of connexin and non-connexin-related hearing loss by ethnic origin, detection by newborn hearing screening, phenotype, neonatal risk factors, and family history. This is the first study to differentiate infants with and without connexin-related hearing loss.
We enrolled 95 infants with hearing loss from whom both exons of Cx26 were sequenced and the Cx30 deletion was assayed. Demographic, family history, newborn hearing screening data, perinatal, and audiologic records were analyzed.
Genetic testing identified biallelic Cx26/30 hearing loss-associated variants in 24.7% of infants with a significantly lower prevalence in Hispanic infants (9.1%). Eighty-two infants underwent newborn hearing screening; 12 infants passed, 3 had connexin-related hearing loss. No differences in newborn hearing screening pass rate, neonatal complications, or hearing loss severity were detected between infants with and without connexin-related hearing loss. Family history correlates with connexin-related hearing loss.
Connexin-related hearing loss occurs in one quarter of infants in an ethnically diverse hearing loss population but with a lower prevalence in Hispanic infants. Not all infants with connexin-related hearing loss fail newborn hearing screening. Family history correlates significantly with connexin-related hearing loss. Genetic testing should not be deferred because of newborn complications. These results will have an impact on genetic testing for infant hearing loss.
以往关于连接蛋白相关听力损失的研究通常报道的是混合年龄组或成年人。为了进一步探讨连接蛋白相关听力损失的流行病学和自然病史，我们在一个种族多样化的3岁以下婴幼儿队列中进行了一项纵向研究。我们的研究比较了有无连接蛋白相关听力损失的婴儿，以检查不同种族来源的连接蛋白和非连接蛋白相关听力损失的患病率差异、新生儿听力筛查的检测情况、表型、新生儿危险因素和家族史。这是第一项区分有无连接蛋白相关听力损失婴儿的研究。
我们招募了95名听力损失婴儿，对其Cx26的两个外显子进行测序，并检测Cx30缺失情况。分析了人口统计学、家族史、新生儿听力筛查数据、围产期和听力学记录。
基因检测在24.7%的婴儿中发现了双等位基因Cx26/30听力损失相关变异，西班牙裔婴儿的患病率显著较低（9.1%）。82名婴儿接受了新生儿听力筛查；12名婴儿通过，3名患有连接蛋白相关听力损失。有无连接蛋白相关听力损失的婴儿在新生儿听力筛查通过率、新生儿并发症或听力损失严重程度方面未发现差异。家族史与连接蛋白相关听力损失相关。
在种族多样化的听力损失人群中，四分之一的婴儿患有连接蛋白相关听力损失，但西班牙裔婴儿的患病率较低。并非所有患有连接蛋白相关听力损失的婴儿新生儿听力筛查都不通过。家族史与连接蛋白相关听力损失显著相关。不应因新生儿并发症而推迟基因检测。这些结果将对婴儿听力损失的基因检测产生影响。
