title: Loss of ZDHHC15 expression in a woman with a balanced translocation t(X;15)(q13.3;cen) and severe mental retardation.
abstract: X-linked mental retardation (XLMR) affects one in 600 males and is highly heterogeneous. We describe here a 29-year-old woman with severe nonsyndromic mental retardation and a balanced reciprocal translocation between chromosomes X and 15 [46,XX,t(X;15)(q13.3;cen)]. Methylation studies showed a 100% skewed X-inactivation in patient-derived lymphocytes indicating that the normal chromosome X is retained inactive. Physical mapping of the breakpoints localised the Xq13.3 breakpoint to within 3.9 kb of the first exon of the ZDHHC15 gene encoding a zinc-finger and a DHHC domain containing product. Expression analysis revealed that different transcript variants of the gene are expressed in brain. ZDHHC15-specific RT-PCR analysis on lymphocytes from the patient revealed an absence of ZDHHC15 transcript variants, detected in control samples. We suggest that the absence of the ZDHHC15 transcripts in this patient contributes to her phenotype, and that the gene is a strong candidate for nonsyndromic XLMR.
authors.affiliation: Department of Genetics and Pathology, Uppsala University, Sweden.
authors.forename: Mahmoud Reza
authors.initials: MR
authors.lastname: Mansouri
authors.forename: Lena
authors.initials: L
authors.lastname: Marklund
authors.forename: Peter
authors.initials: P
authors.lastname: Gustavsson
authors.forename: Edward
authors.initials: E
authors.lastname: Davey
authors.forename: Birgit
authors.initials: B
authors.lastname: Carlsson
authors.forename: Catharina
authors.initials: C
authors.lastname: Larsson
authors.forename: Irene
authors.initials: I
authors.lastname: White
authors.forename: Karl-Henrik
authors.initials: KH
authors.lastname: Gustavson
authors.forename: Niklas
authors.initials: N
authors.lastname: Dahl
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D038901:X-Linked Intellectual Disability / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D014178:Translocation, Genetic; D049951:X Chromosome Inactivation
chemical_list: D004268:DNA-Binding Proteins; C505905:ZDHHC15 protein, human