Split hand/foot malformation due to chromosome 7q aberrations(SHFM1): additional support for functional haploinsufficiency as the causative mechanism.
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.
van Silfhout
Anneke T
AT
Department of Genetics, University Medical Centre Groningen, University of Groningen, The Netherlands.
van den Akker
Peter C
PC
Dijkhuizen
Trijnie
T
Verheij
Joke B G M
JB
Olderode-Berends
Maran J W
MJ
Kok
Klaas
K
Sikkema-Raddatz
Birgit
B
van Ravenswaaij-Arts
Conny M A
CM
D000015:Abnormalities, Multiple / Q000235:genetics*; D002869:Chromosome Aberrations; D002897:Chromosomes, Human, Pair 7; D005260:Female; D005532:Foot Deformities, Congenital / Q000235:genetics*; D006228:Hand Deformities, Congenital / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male