title: Biparental inheritance of chromosomal abnormalities in male twins with non-syndromic mental retardation.
abstract: In a monozygotic twin couple with mental retardation (MR), we identified a maternally inherited inversion and a paternally inherited translocation: 46,XY,inv(10)(p11.2q21.2)mat,t(9;18)(p22;q21.1)pat. The maternally inherited inv(10) was a benign variant without any apparent phenotypical implications. The translocation breakpoint at 9p was within a cluster of interferon α genes and the 18q21 breakpoint truncated ZBTB7C (zinc finger and BTB containing 7C gene). In addition, analyses with array-CGH revealed a 931 kb maternally inherited deletion on chromosome 8q22 as well as an 875 kb maternally inherited duplication on 5p14. The deletion encompasses the RIM2 (Rab3A-interacting molecule 2), FZD6 (Frizzled homolog 6) and BAALC (Brain and Acute Leukemia Gene, Cytoplasmic) genes and the duplication includes the 5' end of the CDH9 (cadherin 9) gene. Exome sequencing did not reveal any additional mutations that could explain the MR phenotype. The protein products of the above mentioned genes are involved in different aspects of brain development and/or maintenance of the neurons which suggest that accumulation of genetic defects segregating from both parents might be the basis of MR in the twins. This hypothesis was further supported by protein interaction analysis.
authors.affiliation: Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen N, Denmark. metteg@sund.ku.dk
authors.forename: Mette
authors.initials: M
authors.lastname: Gilling
authors.forename: Allan
authors.initials: A
authors.lastname: Lind-Thomsen
authors.forename: Yuan
authors.initials: Y
authors.lastname: Mang
authors.forename: Mads
authors.initials: M
authors.lastname: Bak
authors.forename: Morten
authors.initials: M
authors.lastname: Møller
authors.forename: Reinhard
authors.initials: R
authors.lastname: Ullmann
authors.forename: Ulf
authors.initials: U
authors.lastname: Kristoffersson
authors.forename: Vera M
authors.initials: VM
authors.lastname: Kalscheuer
authors.forename: Karen Friis
authors.initials: KF
authors.lastname: Henriksen
authors.forename: Merete
authors.initials: M
authors.lastname: Bugge
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Tümer
authors.forename: Niels
authors.initials: N
authors.lastname: Tommerup
mesh_terms: D000818:Animals; D002648:Child; D002869:Chromosome Aberrations; D056905:Chromosome Breakpoints; D002872:Chromosome Deletion; D058674:Chromosome Duplication; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010641:Phenotype; D025941:Protein Interaction Mapping; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D014178:Translocation, Genetic; D014430:Twins, Monozygotic / Q000235:genetics*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; C110461:ZBTB7C protein, human