TBX3 and TBX5 duplication: A family with an atypical overlapping Holt-Oram/ulnar-mammary syndrome phenotype
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TBX3 and TBX5 duplication: A family with an atypical overlapping Holt-Oram/ulnar-mammary syndrome phenotype. / Cenni, Camille; Andres, Stephanie; Hempel, Maja; Strom, Tim M; Thomas, Ellen; Davies, Angela; Timoney, Norma; Frigiola, Alessandra; Logan, Malcolm; Holder-Espinasse, Muriel.
in: EUR J MED GENET, Jahrgang 64, Nr. 7, 104213, 07.2021.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - TBX3 and TBX5 duplication: A family with an atypical overlapping Holt-Oram/ulnar-mammary syndrome phenotype
AU - Cenni, Camille
AU - Andres, Stephanie
AU - Hempel, Maja
AU - Strom, Tim M
AU - Thomas, Ellen
AU - Davies, Angela
AU - Timoney, Norma
AU - Frigiola, Alessandra
AU - Logan, Malcolm
AU - Holder-Espinasse, Muriel
N1 - Copyright © 2021 Elsevier Masson SAS. All rights reserved.
PY - 2021/7
Y1 - 2021/7
N2 - Holt-Oram syndrome (HOS) is a rare, autosomal dominant heart-hand syndrome caused by mutations in the TBX5 gene. A wide spectrum of TBX5 mutations have been reported previously, most resulting in a null allele leading to haploinsufficiency. TBX5 gene duplications have been previously reported in association with typical and atypical HOS phenotypes. Ulnar-Mammary syndrome (UMS) is a distinct rare, autosomal dominant condition caused by mutations in the TBX3 gene. TBX5 and TBX3 are physically linked in cis on human chromosome 12 and contiguous chromosome 12q24 deletions comprising both TBX5 and TBX3 genes have been previously reported but to our knowledge, duplications have never been described. We report on a large German family with at least 17 affected individuals over 6 generations bearing a duplication at 12q24.21 identified on array-CGH comprising both TBX5 and TBX3 genes. Affected patients are presenting with HOS and UMS symptoms, consisting of variable limb anomalies involving the radial and the ulnar rays and cardiac findings such as congenital heart defects, persistent arterial duct or aortic stenosis, and non-classical symptoms, such as supernumerary nipples and cardiomyopathy. Fluorescence in situ hybridisation confirmed a tandem duplication at the 12q24.21 locus. This is the first report of a contiguous TBX3/TBX5 duplication associated with HOS/UMS phenotype.
AB - Holt-Oram syndrome (HOS) is a rare, autosomal dominant heart-hand syndrome caused by mutations in the TBX5 gene. A wide spectrum of TBX5 mutations have been reported previously, most resulting in a null allele leading to haploinsufficiency. TBX5 gene duplications have been previously reported in association with typical and atypical HOS phenotypes. Ulnar-Mammary syndrome (UMS) is a distinct rare, autosomal dominant condition caused by mutations in the TBX3 gene. TBX5 and TBX3 are physically linked in cis on human chromosome 12 and contiguous chromosome 12q24 deletions comprising both TBX5 and TBX3 genes have been previously reported but to our knowledge, duplications have never been described. We report on a large German family with at least 17 affected individuals over 6 generations bearing a duplication at 12q24.21 identified on array-CGH comprising both TBX5 and TBX3 genes. Affected patients are presenting with HOS and UMS symptoms, consisting of variable limb anomalies involving the radial and the ulnar rays and cardiac findings such as congenital heart defects, persistent arterial duct or aortic stenosis, and non-classical symptoms, such as supernumerary nipples and cardiomyopathy. Fluorescence in situ hybridisation confirmed a tandem duplication at the 12q24.21 locus. This is the first report of a contiguous TBX3/TBX5 duplication associated with HOS/UMS phenotype.
KW - Abnormalities, Multiple/genetics
KW - Breast Diseases/complications
KW - Female
KW - Gene Duplication
KW - Heart Defects, Congenital/complications
KW - Heart Septal Defects, Atrial/complications
KW - Humans
KW - Lower Extremity Deformities, Congenital/complications
KW - Male
KW - Pedigree
KW - Phenotype
KW - T-Box Domain Proteins/genetics
KW - Ulna/abnormalities
KW - Upper Extremity Deformities, Congenital/complications
U2 - 10.1016/j.ejmg.2021.104213
DO - 10.1016/j.ejmg.2021.104213
M3 - SCORING: Journal article
C2 - 33930582
VL - 64
JO - EUR J MED GENET
JF - EUR J MED GENET
SN - 1769-7212
IS - 7
M1 - 104213
ER -