2008 Barcelona - European Society of Human Genetics

Concurrent Sessions
rying BRCA1 mutation, leading to a low frequency of females with a
skewed XCI respect to the general population; ii) an effect of chemotherapy
on XCI status that should be taken into account when analyzing
XCI in cancer patients .
c11.1
Identification of causative mutations, including a ZRS sonic
hedgehog regulatory variant, in an unselected cohort of 203
patients with congenital limb malformations
D. Furniss1,2 , S. Kan1 , P. S. Critchley2 , H. Giele2 , A. O. M. Wilkie1 ;
1 2 Weatherall Institute of Molecular Medicine, Oxford, United Kingdom, Department
of Plastic and Reconstructive Surgery, Oxford, United Kingdom.
Congenital limb malformations (CLMs) are common: major aetiological
factors are genetic mutations and intrauterine disruptions . We
have characterised the causative mutations in an unselected cohort
of patients with CLMs requiring reconstructive surgery . At operation,
blood was taken for DNA extraction and karyotype analysis . Candidate
genes were screened for point mutations using DHPLC and sequencing,
and for deletions by MLPA .
From a cohort of 203 patients, causative genetic changes were identified
in 22 (11%). In addition to 4 chromosome abnormalities, these
comprised mutations in GLI3 (5), HOXD13 (5), the ZRS of SHH (3),
SALL1 (2) and SALL4, TBX5 and ESCO2 (1 each) . Factors that predicted
the discovery of a genetic cause included bilateral malformation,
positive family history, and increasing numbers of limbs affected
(all p