Complex inheritance pattern resembling autosomal recessive inheritance involving a microdeletion in thrombocytopenia-absent radius syndrome.
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).
Klopocki
Eva
E
Institut für Medizinische Genetik, Charité Universitätsmedizin Berlin, Berlin, Germany.
Schulze
Harald
H
Strauss
Gabriele
G
Ott
Claus-Eric
CE
Hall
Judith
J
Trotier
Fabienne
F
Fleischhauer
Silke
S
Greenhalgh
Lynn
L
Newbury-Ecob
Ruth A
RA
Neumann
Luitgard M
LM
Habenicht
Rolf
R
König
Rainer
R
Seemanova
Eva
E
Megarbane
André
A
Ropers
Hans-Hilger
HH
Ullmann
Reinhard
R
Horn
Denise
D
Mundlos
Stefan
S
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*