title: Candidate loci for Zimmermann-Laband syndrome at 3p14.3.
abstract: A male with 46,XY,t(3;17)(p14.3;q24.3) presented with gingival hyperplasia, hypertrichosis, unusually large ears and marked hypertrophy of the nose, characteristic of the Zimmermann-Laband syndrome (ZLS). Other features include large facial bones and mandibles, large protruding upper lip, enlarged fingers and toes, strabismus, and enlarged phallus. Knowledge of a 46,XX,t(3;8)(p21.2;q24.3) reported previously in a mother and daughter with ZLS suggests that the 3p14.3-p21.2 region may contain a gene responsible for ZLS. We have reassessed the chromosome 3 breakpoint region of the t(3;8) and revised its breakpoint location to 3p14.3, based upon an updated human genome sequence assembly. Using fluorescence in situ hybridization (FISH) with BAC clones, we have also identified a breakpoint spanning clone at 3p14.3 in our t(3;17) patient, thereby narrowing the breakpoint to a region of approximately 200 kb. These data suggest that the gene responsible for ZLS is located in 3p14.3 and implicates four likely candidate genes in this region: CACNA2D3, encoding a voltage-dependent calcium channel, LRTM1, a gene of unknown function embedded within CACNA2D3, WNT5A, encoding a secreted signaling protein of the WNT family, and ERC2, which codes for a synapse protein.
authors.affiliation: Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital/Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Hyung-Goo
authors.initials: HG
authors.lastname: Kim
authors.forename: Anne W
authors.initials: AW
authors.lastname: Higgins
authors.forename: Steven R
authors.initials: SR
authors.lastname: Herrick
authors.forename: Shotaro
authors.initials: S
authors.lastname: Kishikawa
authors.forename: Linda
authors.initials: L
authors.lastname: Nicholson
authors.forename: Kerstin
authors.initials: K
authors.lastname: Kutsche
authors.forename: Azra H
authors.initials: AH
authors.lastname: Ligon
authors.forename: David J
authors.initials: DJ
authors.lastname: Harris
authors.forename: Marcy E
authors.initials: ME
authors.lastname: MacDonald
authors.forename: Gail A P
authors.initials: GA
authors.lastname: Bruns
authors.forename: Cynthia C
authors.initials: CC
authors.lastname: Morton
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Quade
authors.forename: James F
authors.initials: JF
authors.lastname: Gusella
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D020746:Calcium Channels, L-Type / Q000235:genetics; D002460:Cell Line; D019457:Chromosome Breakage; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000473:pathology; D003598:Cytoskeletal Proteins; D005347:Fibroblasts; D005885:Gingival Hyperplasia / Q000235:genetics* / Q000473:pathology; D006801:Humans; D006983:Hypertrichosis / Q000235:genetics* / Q000473:pathology; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D011518:Proto-Oncogene Proteins / Q000235:genetics; D013577:Syndrome; D014178:Translocation, Genetic; D051153:Wnt Proteins / Q000235:genetics; D000071818:Wnt-5a Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D020746:Calcium Channels, L-Type; D003598:Cytoskeletal Proteins; C406485:ERC2 protein, human; D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein