title: Complex inheritance pattern resembling autosomal recessive inheritance involving a microdeletion in thrombocytopenia-absent radius syndrome.
abstract: Thrombocytopenia-absent radius (TAR) syndrome is characterized by hypomegakaryocytic thrombocytopenia and bilateral radial aplasia in the presence of both thumbs. Other frequent associations are congenital heart disease and a high incidence of cow's milk intolerance. Evidence for autosomal recessive inheritance comes from families with several affected individuals born to unaffected parents, but several other observations argue for a more complex pattern of inheritance. In this study, we describe a common interstitial microdeletion of 200 kb on chromosome 1q21.1 in all 30 investigated patients with TAR syndrome, detected by microarray-based comparative genomic hybridization. Analysis of the parents revealed that this deletion occurred de novo in 25% of affected individuals. Intriguingly, inheritance of the deletion along the maternal line as well as the paternal line was observed. The absence of this deletion in a cohort of control individuals argues for a specific role played by the microdeletion in the pathogenesis of TAR syndrome. We hypothesize that TAR syndrome is associated with a deletion on chromosome 1q21.1 but that the phenotype develops only in the presence of an additional as-yet-unknown modifier (mTAR).
authors.affiliation: Institut für Medizinische Genetik, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Klopocki
authors.forename: Harald
authors.initials: H
authors.lastname: Schulze
authors.forename: Gabriele
authors.initials: G
authors.lastname: Strauss
authors.forename: Claus-Eric
authors.initials: CE
authors.lastname: Ott
authors.forename: Judith
authors.initials: J
authors.lastname: Hall
authors.forename: Fabienne
authors.initials: F
authors.lastname: Trotier
authors.forename: Silke
authors.initials: S
authors.lastname: Fleischhauer
authors.forename: Lynn
authors.initials: L
authors.lastname: Greenhalgh
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Newbury-Ecob
authors.forename: Luitgard M
authors.initials: LM
authors.lastname: Neumann
authors.forename: Rolf
authors.initials: R
authors.lastname: Habenicht
authors.forename: Rainer
authors.initials: R
authors.lastname: König
authors.forename: Eva
authors.initials: E
authors.lastname: Seemanova
authors.forename: André
authors.initials: A
authors.lastname: Megarbane
authors.forename: Hans-Hilger
authors.initials: HH
authors.lastname: Ropers
authors.forename: Reinhard
authors.initials: R
authors.lastname: Ullmann
authors.forename: Denise
authors.initials: D
authors.lastname: Horn
authors.forename: Stefan
authors.initials: S
authors.lastname: Mundlos
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D040582:Inheritance Patterns; D008297:Male; D008875:Middle Aged; D011884:Radius / Q000002:abnormalities*; D013577:Syndrome; D013921:Thrombocytopenia / Q000235:genetics*