Disruption of the clathrin heavy chain-like gene (CLTCL) associated with features of DGS/VCFS: A balanced (21;22)(p12;q11) translocation

Susan E. Holmes, M. Ali Riazi, Weilong Gong, Heather E. McDermid, Beatrice T. Sellinger, Axin Hua, Feng Chen, Zhili Wang, Guozhang Zhang, Bruce Roe, Iris Gonzalez, Donna M. McDonald-McGinn, Elaine Zackai, Beverly S. Emanuel, Marcia L. Budarf

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)357-367
Number of pages11
JournalHuman molecular genetics
Issue number3
StatePublished - Mar 1997
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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