title: Hemifacial microsomia: progress in understanding the genetic basis of a complex malformation syndrome.
abstract: Hemifacial microsomia (HFM) is a common birth defect involving first and second branchial arch derivatives. The phenotype is extremely variable. In addition to craniofacial anomalies there may be cardiac, vertebral and central nervous system defects. The majority of cases are sporadic, but there is substantial evidence for genetic involvement in this condition, including rare familial cases that exhibit autosomal dominant inheritance. As an approach towards identifying molecular pathways involved in ear and facial development, we have ascertained both familial and sporadic cases of HFM. A genome wide search for linkage in two families with features of HFM was performed to identify the disease loci. In one family data were highly suggestive of linkage to a region of approximately 10.7 cM on chromosome 14q32, with a maximum multipoint lod score of 3.00 between microsatellite markers D14S987 and D14S65. This locus harbours the Goosecoid gene, an excellent candidate for HFM based on mouse expression and phenotype data. Coding region mutations were sought in the familial cases and in 120 sporadic cases, and gross rearrangements of the gene were excluded by Southern blotting. Evidence for genetic heterogeneity is provided by the second family, in which linkage was excluded from this region.
authors.affiliation: Clinical and Molecular Genetics Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: D
authors.initials: D
authors.lastname: Kelberman
authors.forename: J
authors.initials: J
authors.lastname: Tyson
authors.forename: D C
authors.initials: DC
authors.lastname: Chandler
authors.forename: A M
authors.initials: AM
authors.lastname: McInerney
authors.forename: J
authors.initials: J
authors.lastname: Slee
authors.forename: D
authors.initials: D
authors.lastname: Albert
authors.forename: A
authors.initials: A
authors.lastname: Aymat
authors.forename: M
authors.initials: M
authors.lastname: Botma
authors.forename: M
authors.initials: M
authors.lastname: Calvert
authors.forename: J
authors.initials: J
authors.lastname: Goldblatt
authors.forename: E A
authors.initials: EA
authors.lastname: Haan
authors.forename: N G
authors.initials: NG
authors.lastname: Laing
authors.forename: J
authors.initials: J
authors.lastname: Lim
authors.forename: S
authors.initials: S
authors.lastname: Malcolm
authors.forename: S L
authors.initials: SL
authors.lastname: Singer
authors.forename: R M
authors.initials: RM
authors.lastname: Winter
authors.forename: M
authors.initials: M
authors.lastname: Bitner-Glindzicz
mesh_terms: D000015:Abnormalities, Multiple / Q000209:etiology / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D005146:Facial Asymmetry / Q000209:etiology / Q000235:genetics*; D005147:Facial Bones / Q000002:abnormalities*; D005260:Female; D005819:Genetic Markers; D005820:Genetic Testing; D006801:Humans; D008126:Lod Score; D008297:Male; D008310:Malocclusion / Q000209:etiology / Q000235:genetics*; D010375:Pedigree; D013577:Syndrome
chemical_list: D005819:Genetic Markers