title: Description of a large kindred with autosomal dominant inheritance of branchial arch anomalies, hearing loss, and ear pits, and exclusion of the branchio-oto-renal (BOR) syndrome gene locus (chromosome 8q13.3).
abstract: It has been suggested that branchio-oculo-facial (BOF) syndrome, deafness with ear pits, and associated conditions [MIM nos. 125100, 120502], and branchio-oto-renal (BOR) [MIM no. 113650] or Melnick-Fraser syndrome represent phenotypic variants of the BOR syndrome, which is inherited in an autosomal dominant (AD) manner and has variable clinical expression. Recently, the BOR gene was mapped to chromosome region 8q13.3 and its sequence was identified as the human homolog of the Drosophila eyes absent (EYA1) gene. We studied an extended family with AD inheritance of branchial arch anomalies (BAA), hearing loss, and ear pits, whose phenotype differed from that of patients with BOR in that none of the affected members had renal abnormalities or lacrimal duct stenosis. Fifteen affected members were studied; ear pits were present in all of them, whereas hearing loss and other BAA were present in 40 and 20%, respectively. Blood was collected from 31 patients; DNA was extracted by standard methods and amplified using primers from microsatellite sequences flanking the BOR locus on chromosome 8q13.3 (D8S1807, D8S530, and D8S543). Linkage analysis was performed under two models of AD inheritance with different penetrance: 100% and 80%. In both cases, the logarithm of odds (LOD) scores produced were significantly less than -2; exclusion of the 8q13.3 locus was also confirmed by multipoint LOD score analysis. We conclude that, in one large family with AD inheritance of BAA, hearing loss and ear pits, the BOR locus was excluded. This represents the first documentation of heterogeneity in branchio-oto anomalies, syndromes with phenotypes similar to BOR syndrome.
authors.affiliation: Unit on Genetics and Endocrinology, Section on Pediatric Endocrinology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1862, US.
authors.forename: C A
authors.initials: CA
authors.lastname: Stratakis
authors.forename: J P
authors.initials: JP
authors.lastname: Lin
authors.forename: O M
authors.initials: OM
authors.lastname: Rennert
mesh_terms: D001934:Branchial Region / Q000002:abnormalities*; D019280:Branchio-Oto-Renal Syndrome / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D004423:Ear / Q000002:abnormalities*; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D008040:Genetic Linkage; D005819:Genetic Markers; D006311:Hearing Disorders / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009687:Nuclear Proteins; D010375:Pedigree; D017027:Protein Tyrosine Phosphatases; D015534:Trans-Activators / Q000235:genetics
chemical_list: D005819:Genetic Markers; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; C104381:EYA1 protein, human; D017027:Protein Tyrosine Phosphatases