title: Characterization of the complex 7q21.3 rearrangement in a patient with bilateral split-foot malformation and hearing loss.
abstract: We report on complex rearrangements of the 7q21.3 region in a female patient with bilateral split-foot malformation and hearing loss. G-banding karyotype was 46,XX,t(7;15)(q21;q15),t(9;14)(q21;q11.2)dn. By fluorescence, in situ hybridization (FISH), Southern hybridization, and inverse PCR, the 7q21.3 translocation breakpoint was determined at the nucleotide level. The breakpoint did not disrupt any genes, but was mapped to 38-kb telomeric to the DSS1 gene, and 258- and 272-kb centromeric to the DLX6 and DLX5 genes, respectively. It remains possible that the translocation would disrupt the interaction between these genes and their regulatory elements. Interestingly, microarray analysis also revealed an interstitial deletion close to (but not continuous to) the 7q21.3 breakpoint, indicating complex rearrangements within the split-hand/foot malformation 1 (SHFM1) locus in this patient. Furthermore, a 4.6-Mb deletion at 15q21.1-q21.2 adjacent to the 15q15 breakpoint was also identified. Cloning of the deletion junction at 7q21.3 revealed that the 0.8-Mb deletion was located 750-kb telomeric to the translocation breakpoint, encompassing TAC1, ASNS, OCM, and a part of LMTK2. Because TAC1, ASNS, and OCM genes were located on the reported copy number variation regions, it was less likely that the three genes were related to the split-foot malformation. LMTK2 appeared to be a potential candidate gene for SHFM1, but no LMTK2 mutations were found in 29 individuals with SHFM. Further LMTK2 analysis of SHFM patients together with hearing loss is warranted.
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Japan. hsaitsu@yokohama-cu.ac.jp
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
authors.forename: Kenji
authors.initials: K
authors.lastname: Kurosawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kawara
authors.forename: Maki
authors.initials: M
authors.lastname: Eguchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mizuguchi
authors.forename: Naoki
authors.initials: N
authors.lastname: Harada
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kaname
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kano
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Toda
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
mesh_terms: D001483:Base Sequence; D002648:Child; D002871:Chromosome Banding; D019457:Chromosome Breakage; D002897:Chromosomes, Human, Pair 7; D004252:DNA Mutational Analysis; D005260:Female; D005532:Foot Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics*; D017353:Gene Deletion; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D020411:Oligonucleotide Array Sequence Analysis; D020161:Physical Chromosome Mapping; D011859:Radiography; D014178:Translocation, Genetic