Fish mapping of a translocation breakpoint at 6q21 (or q22) in a patient with heterotaxia

Abstract

SummaryHeterotaxia is a congenital lateralization defect of visceral organs. As several single-genes that act on the formation of left-right asymmetry during embryogenesis have been identified in animals, a defect in the similar system may play a role in heterotaxia in man. We previously reported a Japanese girl with heterotaxia associated with a de novo balanced translocation (6;18)(q21 or q22;q21.3 or q22). In the present study, based on a hypothesis that one of the putative situs-determining genes is disrupted at a breakpoint of the translocation, we first isolated a yeast artificial chromosome (YAC) clone covering a breakpoint, 6q21 (or q22) of the translocation. Then, using STSs mapped on the YAC, we isolated bacterial artificial chromosome (BAC) clones spanning the breakpoint. FISH analysis using the BAC clones as probes revealed that the breakpoint is confined to a segment between two STS loci, WI-4066 and the CHLC.GATA6B06.192, within a genetic distance of 1.4 cM. The human connexin43 gene was not disrupted in our patient, although mutations of this gene have been reported in patients with complex heart disease and heterotaxia. The molecular localization of the translocation breakpoint in our patient may contribute to the positional cloning of a putative heterotaxia gene.

Microdeletion of chromosome sub-band 2q37.3 in two patients with abnormal situs viscerum

“…Complex heart defects are common and other clinically significant abnormalities are asplenia, intestinal malrotation, and abnormalities of the biliary system, and also some midline defects of the lumbosacral spine and hindgut. The cytogenetic abnormalities in single cases reported with situs abnormalities are: translocations, t(7;16)(p22;q24) [Warburton, 1991], t(12;13)(q13.1;p13)mat [Wilson et al, 1991], t(6;18)(q21 or q22;q21.3 orq22) [Kato et al, 1997], and t(11;20)(q13.1;q13.13)pat [Freeman et al, 1996]; deletions, del Xq26 [Ferrero et al, 1997], del(18)(qter→p11:) [Kane et al, 1991]; insertion, ins(7;8)(q22;q12q24) [Koiffmann et al, 1993]; inversion, inv(11)(q13q25) [Fukushima et al, 1993], and paternal isodisomy:paternal uniparental disomy, upd(7)pat [Pan et al, 1998]. However, many genes have been implicated in normal and abnormal situs determination.…”

Heterotaxy with left atrial isomerism in a patient with deletion 18p

“…Additionally, a submicroscopic deletion in Xq26 has been found to be associated with familial situs ambiguous [Ferrero et al, 1997]. Many additional chromosomal regions are involved in cytogenetic abnormalities detected in single patients with situs abnormalities, including translocations (7;16)(p22;q24), (12;13)(q13.1;p13)mat, (6;18)(q21;q21.3), (11;20)(q13.1;13.13)pat, insertion (7;8)(q22;q12q24), inversion (11)(q13q25), and paternal uniparental disomy 7 [Warburton, 1991; Wilson et al, 1991; Koiffmann et al, 1993; Fukushima et al, 1993; Freeman et al, 1996; Kato et al, 1997; Pan et al, 1998]. Chromosome abnormalities may suggest localizations of putative gene(s) for lateralization defects.…”

Recurrent involvement of chromosomal region 6q21 in heterotaxy

“…Another patient with heterotaxy and a de novo balanced translocation (6;18)(q21;q21.3 or q22) was reported by Kato et al [1996]. In that patient, the position of the breakpoint was localized between two STS loci, WI‐4066 and CHLC.GATA6B06.192 contained in YAC 798G12, with a size of 910 kb [Kato et al, 1997]. DNA from this YAC was used in a FISH analysis on metaphase spreads of the patient to determine the position of the translocation with respect to the breakpoint in the previously reported patient.…”

“…We present a patient with a de novo apparently balanced reciprocal translocation, involving chromosome band 6q21, which has been implicated in situs inversus before [Kato et al, 1996, Kato et al, 1997].…”