title: Disruption of the clathrin heavy chain-like gene (CLTCL) associated with features of DGS/VCFS: a balanced (21;22)(p12;q11) translocation.
abstract: The smallest region of deletion overlap in the patients we have studied defines a DIGeorge syndrome/velocardiofacial syndrome (DGS/VCFS) minimal critical region (MDGCR) of approximately 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.
authors.affiliation: Division of Human Genetics and Molecular Biology, Children's Hospital of Philadelphia, PA 19104, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Holmes
authors.forename: M A
authors.initials: MA
authors.lastname: Riazi
authors.forename: W
authors.initials: W
authors.lastname: Gong
authors.forename: H E
authors.initials: HE
authors.lastname: McDermid
authors.forename: B T
authors.initials: BT
authors.lastname: Sellinger
authors.forename: A
authors.initials: A
authors.lastname: Hua
authors.forename: F
authors.initials: F
authors.lastname: Chen
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Zhang
authors.forename: B
authors.initials: B
authors.lastname: Roe
authors.forename: I
authors.initials: I
authors.lastname: Gonzalez
authors.forename: D M
authors.initials: DM
authors.lastname: McDonald-McGinn
authors.forename: E
authors.initials: E
authors.lastname: Zackai
authors.forename: B S
authors.initials: BS
authors.lastname: Emanuel
authors.forename: M L
authors.initials: ML
authors.lastname: Budarf
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D001483:Base Sequence; D002478:Cells, Cultured; D002675:Child, Preschool; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D002966:Clathrin / Q000235:genetics*; D033922:Clathrin Heavy Chains; D003001:Cloning, Molecular; D019465:Craniofacial Abnormalities / Q000235:genetics; D004062:DiGeorge Syndrome / Q000235:genetics*; D006330:Heart Defects, Congenital / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D008969:Molecular Sequence Data; D013577:Syndrome; D014178:Translocation, Genetic
chemical_list: D002966:Clathrin; D033922:Clathrin Heavy Chains