A locus for asphyxiating thoracic dystrophy, ATD, maps to chromosome 15q13
- N V Morgan1,
- C Bacchelli2,
- P Gissen1,3,
- J Morton4,
- G B Ferrero5,
- M Silengo5,
- P Labrune6,
- I Casteels7,
- C Hall8,
- P Cox9,
- D A Kelly3,
- R C Trembath10,
- P J Scambler2,
- E R Maher1,
- F R Goodman2,
- C A Johnson1
- 1Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham Medical School, Birmingham B15 2TT, UK
- 2Molecular Medicine Unit, Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK
- 3Children’s Liver Unit, Princess of Wales Children’s Hospital, Steelhouse Lane, Birmingham B4 6NH, UK
- 4West Midlands Regional Clinical Genetics Service, Birmingham Women’s Hospital, Birmingham, B15 2TG, UK
- 5Dipartimento di Scienze Pediatriche e dell’Adolescenza, Università degli Studi di Torino, Piazza Polonia 94, 10126 Torino, Italy
- 6Service de Pédiatrie, Hôf.pital Antoine-Béclére, 157 Rue de la Porte-de-Trivaux BP 405, 92141 Clamart, France
- 7Department of Paediatric Ophthalmology, St Rafael University Hospital, Capucijnenvoer 33, 3000 Leuven, Belgium
- 8Department of Radiology, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London WC1N 3JH, UK
- 9Department of Pathology, Birmingham Women’s Hospital, Birmingham B15 2TG, UK
- 10Division of Medical Genetics, Departments of Medicine and Genetics, University of Leicester, Leicester LE1 7RH, UK
- Correspondence to: Dr C A Johnson, Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham Medical School, Birmingham B15 2TT, UK; c.a.johnson{at}bham.ac.uk
- Received 1 March 2003
- Accepted 3 March 2003
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 ϑ=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.
