title: A locus for asphyxiating thoracic dystrophy, ATD, maps to chromosome 15q13.
abstract: Asphyxiating thoracic dystrophy (ATD), or Jeune syndrome, is a multisystem autosomal recessive disorder associated with a characteristic skeletal dysplasia and variable renal, hepatic, pancreatic, and retinal abnormalities. We have performed a genome wide linkage search using autozygosity mapping in a cohort of four consanguineous families with ATD, three of which originate from Pakistan, and one from southern Italy. In these families, as well as in a fifth consanguineous family from France, we localised a novel ATD locus (ATD) to chromosome 15q13, with a maximum cumulative two point lod score at D15S1031 (Zmax=3.77 at theta=0.00). Five consanguineous families shared a 1.2 cM region of homozygosity between D15S165 and D15S1010. Investigation of a further four European kindreds, with no known parental consanguinity, showed evidence of marker homozygosity across a similar interval. Families with both mild and severe forms of ATD mapped to 15q13, but mutation analysis of two candidate genes, GREMLIN and FORMIN, did not show pathogenic mutations.
authors.affiliation: Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham Medical School, Birmingham B15 2TT, UK.
authors.forename: N V
authors.initials: NV
authors.lastname: Morgan
authors.forename: C
authors.initials: C
authors.lastname: Bacchelli
authors.forename: P
authors.initials: P
authors.lastname: Gissen
authors.forename: J
authors.initials: J
authors.lastname: Morton
authors.forename: G B
authors.initials: GB
authors.lastname: Ferrero
authors.forename: M
authors.initials: M
authors.lastname: Silengo
authors.forename: P
authors.initials: P
authors.lastname: Labrune
authors.forename: I
authors.initials: I
authors.lastname: Casteels
authors.forename: C
authors.initials: C
authors.lastname: Hall
authors.forename: P
authors.initials: P
authors.lastname: Cox
authors.forename: D A
authors.initials: DA
authors.lastname: Kelly
authors.forename: R C
authors.initials: RC
authors.lastname: Trembath
authors.forename: P J
authors.initials: PJ
authors.lastname: Scambler
authors.forename: E R
authors.initials: ER
authors.lastname: Maher
authors.forename: F R
authors.initials: FR
authors.lastname: Goodman
authors.forename: C A
authors.initials: CA
authors.lastname: Johnson
mesh_terms: D001237:Asphyxia / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D015331:Cohort Studies; D003241:Consanguinity; D005260:Female; D005602:France; D005819:Genetic Markers; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007558:Italy; D008297:Male; D010009:Osteochondrodysplasias / Q000235:genetics*; D010154:Pakistan; D010375:Pedigree; D013909:Thorax / Q000002:abnormalities*
chemical_list: D005819:Genetic Markers