A locus for asphyxiating thoracic dystrophy, ATD, maps to chromosome 15q13.
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.
Morgan
N V
NV
Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham Medical School, Birmingham B15 2TT, UK.
Bacchelli
C
C
Gissen
P
P
Morton
J
J
Ferrero
G B
GB
Silengo
M
M
Labrune
P
P
Casteels
I
I
Hall
C
C
Cox
P
P
Kelly
D A
DA
Trembath
R C
RC
Scambler
P J
PJ
Maher
E R
ER
Goodman
F R
FR
Johnson
C A
CA
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*
D005819:Genetic Markers