A microdeletion proximal of the critical deletion region is associated with mild Wolf-Hirschhorn syndrome.

[wolf-hirschhorn syndrome]

It is generally accepted that the facial phenotype of Wolf-Hirschhorn syndrome is caused by deletions of either Wolf -Hirschhorn critical regions 1 or 2 (WHSCR 1 -2 ). Here , we identify a 432 â€‰kb deletion located 600 â€‰kb proximal to both WHSCR 1 -2 in a patient with a WHS facial phenotype . Seven genes are underlying this deletion region including FAM 193 a , ADD 1 , NOP 14 , GRK 4 , MFSD 10 , SH 3 BP 2 , TNIP 2 . The clinical diagnosis of WHS facial phenotype was confirmed by 3 D facial analysis using dense surface modeling . Our results suggest that the WHSCR 1 -2 flanking sequence contributes directly or indirectly to the severity of WHS . Sequencing the Wolf-Hirschhorn syndrome candidate 1 and 2 genes did not reveal any mutations . Long range position effects of the deletion that could influence gene expression within the WHSCR were excluded in EBV cell lines derived from patient lymphoblasts . We hypothesize that either (1 ) this locus harbors regulatory sequences which affect gene expression in the WHSCR 1 -2 in a defined temporal and spatial developmental window or (2 ) that this locus is additive to deletions of WHSCR 1 -2 increasing the phenotypic expression .