FISH and array‐CGH analysis of a complex chromosome 3 aberration suggests that loss of CNTN4 and CRBN contributes to mental retardation in 3pter deletions

Abstract Imbalances of 3p telomeric sequences cause 3p− and trisomy 3p syndrome, respectively, showing distinct, but also shared clinical features. No causative genes have been identified in trisomy 3p patients, but for the 3p− syndrome, there is growing evidence that monosomy for one or more of four genes at 3pter, CHL1 , CNTN4 , CRBN , and MEGAP/srGAP3 , may play a causative role. We describe here an analysis of a complex chromosome 3p aberration in a severely mentally retarded patient that revealed two adjacent segments with different copy number gains and a distal deletion. The deletion in this patient included the loci for CHL1 , CNTN4 , and CRBN , and narrowed the critical segment associated with the 3p− syndrome to 1.5 Mb, including the loci for CNTN4 and CRBN . We speculate that the deletion contributes more to this patient's phenotype than the gains that were observed. We suggest that 3p− syndrome associated features are primarily caused by loss of CNTN4 and CRBN , with loss of CHL1 probably having an additional detrimental effect on the cognitive functioning of the present patient. © 2006 Wiley‐Liss, Inc.