Familial transmission of oculoauriculovertebral spectrum (Goldenhar syndrome) is not due to mutations in either EYA1 or SALL1

Genome-Wide Scanning Reveals Complex Etiology of Oculo-Auriculo-Vertebral Spectrum

“…Mild hemifacial microsomia was noted in two affected family members (patients 21 and 32), while epibulbar dermoid, vertebral anomalies, and micrognathia were only noted in patients 34, 32 and 35, respectively. Although each patient has milder manifestations when compared with sporadic cases, their diagnosis as OAVS is most likely in this family (Tasse et al 2005), which supports the extremely heterogeneous phenotype of this disorder even within siblings (Tsai and Tsai 1993;Stoll et al 1998;Tasse et al 2007;Goodin et al 2009;Vendramini-Pittoli and Kokitsu-Nakata 2009).…”

“…Maternal use of medications (Jacobsson and Granstrom 1997;Johnston and Bronsky 1995) and maternal diabetes (Wang et al 2002) contribute to infants with OAVS, which suggests that nongenetic factors play a role in the development of OAVS. Nevertheless, chromosomal aberrations (Engiz et al 2007;Balci et al 2006;Choong et al 2003;Descartes 2006;Josifova et al 2004;Ala-Mello et al 2008;Xu et al 2008;Rooryck et al 2009) and the identification of several families with autosomal dominant (Tsai and Tsai 1993;Stoll et al 1998;Tasse et al 2007;Goodin et al 2009;Vendramini-Pittoli and Kokitsu-Nakata 2009) or recessive inheritance (Kaye et al 1992) indicate that OAVS has a hereditary basis.…”

Oculo-auriculo-vertebral spectrum: Clinical and molecular analysis of 51 patients

“…OGT CytoSure ISCA v2 (8x60k) were used for some of the samples using the methodology described in the manufacturer's instructions (Oxford Gene Technology), and analysed using CytoSure Interpret Software using the analysis criteria described above. (* only samples 16,17,19 and 20 were analysed using the Agilent SurePrint G3 180K arrays)…”

“…Moreover, clinical studies have shown that, following careful history and clinical examination of the relatives of probands with OAVS, up to 45% of "unaffected" relatives do have minor OAVS manifestations [13]. Reports of familial cases following Mendelian inheritance [4,[14][15][16][17], as well as evidence for genetic linkage in two families [18,19], and the presence of OAVS features in patients with various chromosomal aberrations and genomic imbalances [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38], all suggest that some cases of OAVS have a genetic basis. Environmental causes have also been suggested, particularly twinning, assisted reproductive techniques and maternal pre-pregnancy diabetes [1,3].…”

“…Characteristic clinical features of OAVS Patients with OAVS at different ages, presenting facial asymmetry/ hemifacial microsomia of different severities; and microtia and/or other ear anomalies. Map of OAVS loci Candidate genetic loci for OAVS that been suggested by the identification of chromosomal anomalies in patients with phenotypic characteristics of this spectrum (in red); by the identification of the breakpoints in apparently balanced chromosomal rearrangements (in green); by the presence of chromosomal mosaicism in individuals with OAVS features (in orange); by genome wide search forlinkage in families (in purple -full and, less convincingly due to a non-significant LOD score, in purple ---dashed); and by high density oligonucleotide array-CGH (blue)[2,7,8,[12][13][14][15][16][17][18][19][20][21][22]; chromosome 22…”