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

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.

  • Jeune syndrome
  • asphyxiating thoracic dystrophy
  • autozygosity mapping

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