title: Identification of a second HOXA2 nonsense mutation in a family with autosomal dominant non-syndromic microtia and distinctive ear morphology.
abstract: 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.
authors: Mendel Laboratory, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy.
authors: F
authors: F
authors: Piceci
authors: Laboratory of Medical Genetics, Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, Rome, Italy.
authors: S
authors: S
authors: Morlino
authors: Laboratory of Medical Genetics, Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, Rome, Italy.
authors: M
authors: M
authors: Castori
authors: Division of Neonatology and Neonatal Intensive Care, San Camillo-Forlanini Hospital, Rome, Italy.
authors: E
authors: E
authors: Buffone
authors: Mendel Laboratory, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy.
authors: A
authors: A
authors: De Luca
authors: Laboratory of Medical Genetics, Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, Rome, Italy.
authors: P
authors: P
authors: Grammatico
authors: Mendel Laboratory, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy.
authors: V
authors: V
authors: Guida
mesh_terms: D065817:Congenital Microtia / Q000209:etiology / Q000235:genetics*; D004423:Ear / Q000002:abnormalities; D005260:Female; D005799:Genes, Dominant; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D011247:Pregnancy
chemical_list: C520321:HOXA2 protein, human; D018398:Homeodomain Proteins
keywords: HOXA2; genotype-phenotype correlation; microtia