TY - JOUR
T1 - Split hand/foot malformation due to chromosome 7q aberrations(SHFM1)
T2 - additional support for functional haploinsufficiency as the causative mechanism
AU - van Silfhout, Anneke T.
AU - van den Akker, Peter C.
AU - Dijkhuizen, Trijnie
AU - Verheij, Joke B. G. M.
AU - Olderode-Berends, Maran J. W.
AU - Kok, Klaas
AU - Sikkema-Raddatz, Birgit
AU - van Ravenswaaij-Arts, Conny M. A.
PY - 2009/11
Y1 - 2009/11
N2 - We report on three patients with split hand/foot malformation type 1 (SHFM1). We detected a deletion in two patients and an inversion in the third, all involving chromosome 7q21q22. We performed conventional chromosomal analysis, array comparative genomic hybridization and fluorescence in situ hybridization. Both deletions included the known genes associated with SHFM1 (DLX5, DLX6 and DSS1), whereas in the third patient one of the inversion break points was located just centromeric to these genes. These observations confirm that haploinsufficiency due to either a simultaneous deletion of these genes or combined downregulation of gene expression due to a disruption in the region between these genes and a control element could be the cause of the syndrome. We review previously reported studies that support this hypothetical mechanism. European Journal of Human Genetics (2009) 17, 1432-1438; doi:10.1038/ejhg.2009.72; published online 29 April 2009
AB - We report on three patients with split hand/foot malformation type 1 (SHFM1). We detected a deletion in two patients and an inversion in the third, all involving chromosome 7q21q22. We performed conventional chromosomal analysis, array comparative genomic hybridization and fluorescence in situ hybridization. Both deletions included the known genes associated with SHFM1 (DLX5, DLX6 and DSS1), whereas in the third patient one of the inversion break points was located just centromeric to these genes. These observations confirm that haploinsufficiency due to either a simultaneous deletion of these genes or combined downregulation of gene expression due to a disruption in the region between these genes and a control element could be the cause of the syndrome. We review previously reported studies that support this hypothetical mechanism. European Journal of Human Genetics (2009) 17, 1432-1438; doi:10.1038/ejhg.2009.72; published online 29 April 2009
KW - split hand/foot malformation (SHFM)
KW - chromosome 7q21q22
KW - DLX5
KW - DLX6
KW - DSS1
KW - HAND FOOT MALFORMATION
KW - LIMB DEVELOPMENT
KW - CANDIDATE GENE
KW - P63 GENE
KW - LOCUS
KW - EXPRESSION
KW - REARRANGEMENT
KW - FAMILY
KW - DLX5
KW - MUTATIONS
U2 - 10.1038/ejhg.2009.72
DO - 10.1038/ejhg.2009.72
M3 - Article
SN - 1018-4813
VL - 17
SP - 1432
EP - 1438
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 11
ER -