Piceci F, Morlino S, Castori M, Buffone E, De Luca A, Grammatico P, Guida V
Mendel Laboratory, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy.
Laboratory of Medical Genetics, Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, Rome, Italy.
Clin Genet. 2017 May;91(5):774-779. doi: 10.1111/cge.12845. Epub 2016 Sep 13.
Microtia is a congenital defect affecting external ears, which appear smaller and sometimes malformed. Here we describe a five-generation family with isolated bilateral microtia segregating as an autosomal dominant trait. Similar features have been previously observed in an autosomal dominant family with non-syndromic microtia and hearing loss segregating with a HOXA2 nonsense variant. HOXA2 biallelic mutations were also described in an inbreed family with autosomal recessive microtia, hearing impairment and incomplete cleft palate. In our family, sequence analysis detected a heterozygous protein truncating nonsense variant [c.670G>T, p.(Glu224*)] segregating in all affected individuals and absent in public databases. This study confirms the role of HOXA2 gene in dominant isolated microtia and contribute to further define the dysmorphogenetic effect of this gene on ear development.
小耳症是一种影响外耳的先天性缺陷，外耳会显得较小，有时还会畸形。在此，我们描述了一个五代家族，该家族中孤立性双侧小耳症作为常染色体显性性状进行分离。先前在一个常染色体显性家族中也观察到了类似特征，该家族中，非综合征性小耳症和听力损失与一个HOXA2无义变异共同分离。在一个患有常染色体隐性小耳症、听力障碍和不完全腭裂的近亲家族中，也描述了HOXA2双等位基因突变。在我们的家族中，序列分析检测到一个杂合的蛋白质截短无义变异[c.670G>T, p.(Glu224*)]，该变异在所有受影响个体中分离，且在公共数据库中不存在。本研究证实了HOXA2基因在显性孤立性小耳症中的作用，并有助于进一步明确该基因对耳部发育的畸形发生效应。
