Loss of ZDHHC15 expression in a woman with a balanced translocation t(X;15)(q13.3;cen) and severe mental retardation

• Published in: European journal of human genetics : EJHG Vol. 13; no. 8; pp. 970 - 977
• Main Authors: MANSOURI, Mahmoud Reza, MARKLUND, Lena, GUSTAVSSON, Peter, DAVEY, Edward, CARLSSON, Birgit, LARSSON, Catharina, WHITE, Irene, GUSTAVSON, Karl-Henrik, DAHL, Niklas
• Format: Journal Article
• Language: English
• Published: Avenel, NJ Nature Publishing 01-08-2005; Nature Publishing Group
• Subjects: Adult; Adult and adolescent clinical studies; Amino Acid Sequence; Base Sequence; Biological and medical sciences; Chromosome aberrations; Chromosome Mapping; Chromosomes, Human, Pair 15; DNA Methylation; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; DNA-Binding Proteins/genetics/metabolism; Female; General aspects. Genetic counseling; Humans; Intellectual deficiency; Medical genetics; Medical sciences; MEDICIN; Medicin och hälsovetenskap; MEDICINE; Mental Retardation, X-Linked - genetics; Mental Retardation, X-Linked - metabolism; Molecular Sequence Data; Mutation; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Translocation, Genetic; X Chromosome Inactivation; Chromosomal aberration; Human; Sex linked character; Loss; Developmental disorder; Gene expression; Mental retardation; nonsyndromic X-linked mental retardation; Genetic disease; ZDHHC15; Intellectual deficiency; balanced reciprocal translocation; Abnormal chromosome; Genetics; X-Chromosome; Woman; Severe; Chromosome translocation; Translocation; Mental Retardation; Genetic; Chromosomes; X-Linked/genetics/metabolism; Pair 15
• ISSN: 1018-4813; 1476-5438; 1476-5438
• DOI: 10.1038/sj.ejhg.5201445

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.