De novo 46,XX,t(6;7)(q27;q11;23) associated with severe cardiovascular manifestations characteristic of supravalvular aortic stenosis and Williams syndrome

Abstract

Supravalvular aortic stenosis may present as an isolated finding or as part of Williams syndrome. Williams syndrome is a contiguous gene syndrome associated with neurodevelopmental and multisystemic manifestations caused by hemizygous deletion at 7q11.23. We report on the prenatal and histopathological findings in a patient with a chromosome translocation involving the Williams syndrome critical region. The initial abnormality on fetal ultrasound was hydrops fetalis detected at 30 weeks and echocardiography showed narrowing of the aorta and the pulmonary arteries. The baby died shortly after delivery and an autopsy revealed diffuse tubular thickening with luminal narrowing of the aorta, aortic branches, and the pulmonary arteries. Histopathology showed dysplasia of the media with reduced elastic content and "cartwheel" arrangement of collagen, elastic, and muscle fascicles. The karyotype was 46,XX,t(6;7)(q27;q11.23). Three signals were detected using the Oncor fluorescent in situ hybridization probe for elastin-Williams syndrome (WSCR) suggesting that the break in chromosome 7 is within the elastin-Williams gene. This patient is of special interest because of the prenatal presentation and the chromosomal translocation involving the elastin-Williams syndrome locus.

A novel PAX5-ELN fusion protein identified in B-cell acute lymphoblastic leukemia acts as a dominant negative on wild-type PAX5

“…33 Von Dadelszen et al reported a case of SVAS with a t(6;7)(q27;q11;23) translocation and with the same breakpoint on ELN, but with different breakpoints on chromosome 6. 34 In 2002, Duba et al 35 described 5 patients with the same balanced translocation t(7;16)(q11.23;q13) associated with a variable expression of WBS. This translocation disrupts the ELN gene within intron 5 and creates a fusion gene with intron 1 of the TM7XN1 gene.…”

Characterisation of a non-recurrent familial translocation t(7;9)(q11.23;p24.3) points to a recurrent involvement of the Williams–Beuren syndrome region in chromosomal rearrangements

“…Additional evidence that the 7q11.2 region is prone to rearrangements has been provided by its involvement in several rearrangements such as deletions causing WBS and non-recurrent constitutional translocations, t(6;7)(p21.1;q11.23) and t(6;7)(p27;q11.23) causing SVAS [MIM 185500], t(7;16)(q11.23;q13) causing WBS by disrupting the Elastin gene (Morris et al 1993;von Dadelszen et al 2000;Duba et al 2002). The t(7;9)(q11.23;p24) translocation presented here does not disrupt the Elastin gene in a subject showing a normal phenotype.…”

“…Other than these features, the molecular mechanisms underlying non-recurrent chromosomal rearrangements are often unknown or are simply called ''mediated by random events'', even if some of them seem to reflect susceptibility to DNA rearrangements stimulated by genomic architecture (Inoue et al 2002;Stankiewicz et al 2003). Evidence for the involvement of LCR-rich regions in both recurrent segmental aneusomies and recurrent or non-recurrent translocations has been reported for chromosomal regions 17p11.2-p12, 22q11 and 7q11.23 (Stankiewicz et al 2003;Hill et al 2000;Morris et al 1993;von Dadelszen et al 2000;Duba et al 2002). It is worth noting that 17p11.2-p12 LCRs are implicated in the deletion causing Smith-Magenis [SMS (MIM 182290)] and hereditary neuropathy with liability to pressure palsies [HNPP (MIM 162500)] (Chen et al 1997;Reiter et al 1996), and in the duplication of the same region causing Charcot-Marie-Tooth type 1A (CMT1A [MIM 118220]) and dup(17)(p11.2p11.2) syndrome (Chance et al 1994;Potocki et al 2000).…”

The elastin gene is disrupted in a family with a balanced translocation t(7;16)(q11.23;q13) associated with a variable expression of the Williams-Beuren syndrome

“…There are two reports of chromosomal translocations involving the 7q11.23 region associated with SVAS and`atypical' WBS. 29 One sporadic patient with a translocation t(6;7)(q27;q11.23), SVAS and severe hydrops fetalis has been reported. 29 Based on FISH-analysis the chromosome 7 breakpoint in this patient was speculated to disrupt the elastin gene but no rigorous molecular evidence was provided.…”

“…29 One sporadic patient with a translocation t(6;7)(q27;q11.23), SVAS and severe hydrops fetalis has been reported. 29 Based on FISH-analysis the chromosome 7 breakpoint in this patient was speculated to disrupt the elastin gene but no rigorous molecular evidence was provided. Further it was not possible to distinguish whether this patient had isolated SVAS or WBS given the degree of body oedema and the early gestational age of the patient.…”