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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
Author(s) -
Dijkhuizen Trijnie,
van Essen Ton,
van der Vlies Pieter,
Verheij Joke B.G.M.,
SikkemaRaddatz Birgit,
van der Veen Anneke Y.,
GerssenSchoorl Klasien B.J.,
Buys Charles H.C.M.,
Kok Klaas
Publication year - 2006
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.31487
Subject(s) - genetics , biology , phenotype , monosomy , chromosome , trisomy , chromosome 4 , gene , fish <actinopterygii> , karyotype , fishery
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.