Premium
Beckwith–Wiedemann syndrome and long QT syndrome due to familial‐balanced translocation t(11;17)(p15.5;q21.3) involving the KCNQ1 gene
Author(s) -
Kaltenbach S,
Capri Y,
Rossignol S,
Denjoy I,
Soudée S,
Aboura A,
Baumann C,
Verloes A
Publication year - 2013
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12038
Subject(s) - chromosomal translocation , beckwith–wiedemann syndrome , genetics , long qt syndrome , allele , biology , aunt , breakpoint , uniparental disomy , cousin , gene , chromosome , medicine , karyotype , dna methylation , qt interval , history , gene expression , archaeology , sociology , anthropology
We report a child with Beckwith–Wiedemann syndrome ( BWS ) as the consequence of an apparently balanced, maternally inherited reciprocal translocation t(11;17)(p15.5;q21.3). His mother and aunt, who inherited the translocation from their father, did not have BWS . At birth, long QT syndrome ( LQTS ) was diagnosed in this child and, secondarily, among apparently healthy family members carrying the translocation. By FISH analysis, the breakpoint in 11p15.5 interrupts the KCNQ1 gene between exons 2 and 10 and causes a loss of methylation of the IC2 (and thus BWS ) on the maternally inherited der(11) chromosome. To explain the presence of LQTS segregating with the t(11;17) translocation in this family, we hypothesize that the translocation that interrupts KCNQ1 allow translation of an abnormal short allele that interferes in a dominant negative way with the normal isoform 1 of KCNQ1 in the heart (where this allele is not subject to parental imprint). This appears to be the first report of BWS with congenital LQTS , which should be considered as a rare but serious complication to be searched systematically in patients with BWS due to 11p15 rearrangements.