TY - JOUR
T1 - 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
AU - Dijkhuizen, Trijnie
AU - van Essen, Ton
AU - van der Vlies, Pieter
AU - Verheij, Joke B. G. M.
AU - Sikkema-Raddatz, Birgit
AU - van der Veen, Anneke Y.
AU - Gerssen-Schoorl, Klasien B. J.
AU - Buys, Charles H. C. M.
AU - Kok, Klaas
PY - 2006/11/15
Y1 - 2006/11/15
N2 - 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. (c) 2006 Wiley-Liss, Inc.
AB - 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. (c) 2006 Wiley-Liss, Inc.
KW - array-CGH analysis
KW - mental retardation
KW - CNTN4
KW - CHL1
KW - CRBN
KW - 3p-syndrome
KW - trisomy 3p syndrome
KW - MOLECULAR CHARACTERIZATION
KW - INVERTED DUPLICATION
KW - PRENATAL-DIAGNOSIS
KW - PARTIAL TRISOMY
KW - SHORT ARM
KW - GENE
KW - 3P
KW - PATIENT
KW - 3P-SYNDROME
KW - MONOSOMY
U2 - 10.1002/ajmg.a.31487
DO - 10.1002/ajmg.a.31487
M3 - Article
SN - 1552-4825
VL - 140A
SP - 2482
EP - 2487
JO - American Journal of Medical Genetics. Part A
JF - American Journal of Medical Genetics. Part A
IS - 22
ER -