TY - JOUR
T1 - Disruption of the clathrin heavy chain-like gene (CLTCL) associated with features of DGS/VCFS
T2 - A balanced (21;22)(p12;q11) translocation
AU - Holmes, Susan E.
AU - Riazi, M. Ali
AU - Gong, Weilong
AU - McDermid, Heather E.
AU - Sellinger, Beatrice T.
AU - Hua, Axin
AU - Chen, Feng
AU - Wang, Zhili
AU - Zhang, Guozhang
AU - Roe, Bruce
AU - Gonzalez, Iris
AU - McDonald-McGinn, Donna M.
AU - Zackai, Elaine
AU - Emanuel, Beverly S.
AU - Budarf, Marcia L.
N1 - Funding Information:
The authors would like to thank Dr Jim Sylvester for helpful discussions and Dr H.H. Kazazian Jr for helpful discussions and critical reading of the manuscript. We would also like to acknowledge Karen Romanyk, Jennifer Feuer, Yvonne Tatsumura, Joelle Collins and John Russell for their technical help, and Dr Vahe Bedian at the University of Pennsylvania Sequencing Facility for sequencing of plasmid and phage clones and PCR products. The chromosome 22 cosmid library, LL22NCO3, was obtained from Lawrence Livermore National Laboratory, and the Sanger Center provided the fosmid f39E1. S.E.H. was partially supported by a postdoctoral fellowship from Sandoz Corporation. Further funding for this research was provided by the Medical Research Council of Canada (H.E.M.), the Mental Retardation and Disabilities Research center (HD26979) (B.S.E.) and grants from the National Center for Human Genome Research (HG00425) (B.S.E., M.L.B.), National Institute for Deafness and Communication Disorders (DC02027) (M.L.B., B.S.E., B.R.) and National Heart, Lung, and Blood Institute (HL51533) (M.L.B., B.S.E., B.R.), of the NIH, USA.
PY - 1997/3
Y1 - 1997/3
N2 - The smallest region of deletion overlap in the patients we have studied defines a DiGeorge syndrome/velocardio-facial syndrome (DGSNCFS) minimal critical region (MDGCR) of -250 kb within 22q11. A de novo constitutional balanced translocation has been identified within the MDGCR. The patient has some features which have been reported in individuals with DGS/VCFS, including: facial dysmorphia, mental retardation, long slender digits and genital anomalies. We have cloned the breakpoint of his translocation and shown that it interrupts the clathrin heavy chain-like gene (CLTCL) within the MDGCR. The breakpoint of the translocation partner is in a repeated region telomeric to the rDNA cluster on chromosome 21p. Therefore, it is unlikely that the patient's findings are caused by interruption of sequences on 21p. The chromosome 22 breakpoint disrupts the 3' coding region of the CLTCL gene and leads to a truncated transcript, strongly suggesting a role for this gene in the features found in this patient. Further, the patient's partial DGS/VCFS phenotype suggests that additional features of DGS/VCFS may be attributed to other genes in the MDGCR. Thus, haploinsufficiency for more than one gene in the MDGCR may be etiologic for DGS/VCFS.
AB - The smallest region of deletion overlap in the patients we have studied defines a DiGeorge syndrome/velocardio-facial syndrome (DGSNCFS) minimal critical region (MDGCR) of -250 kb within 22q11. A de novo constitutional balanced translocation has been identified within the MDGCR. The patient has some features which have been reported in individuals with DGS/VCFS, including: facial dysmorphia, mental retardation, long slender digits and genital anomalies. We have cloned the breakpoint of his translocation and shown that it interrupts the clathrin heavy chain-like gene (CLTCL) within the MDGCR. The breakpoint of the translocation partner is in a repeated region telomeric to the rDNA cluster on chromosome 21p. Therefore, it is unlikely that the patient's findings are caused by interruption of sequences on 21p. The chromosome 22 breakpoint disrupts the 3' coding region of the CLTCL gene and leads to a truncated transcript, strongly suggesting a role for this gene in the features found in this patient. Further, the patient's partial DGS/VCFS phenotype suggests that additional features of DGS/VCFS may be attributed to other genes in the MDGCR. Thus, haploinsufficiency for more than one gene in the MDGCR may be etiologic for DGS/VCFS.
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U2 - 10.1093/hmg/6.3.357
DO - 10.1093/hmg/6.3.357
M3 - Article
C2 - 9147638
AN - SCOPUS:8044250300
SN - 0964-6906
VL - 6
SP - 357
EP - 367
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 3
ER -