Characterization of a 16 Mb interstitial chromosome 7q21 deletion by tiling path array CGH

Abstract

We report on a 42-year-old female patient with an interstitial 16 Mb deletion in 7q21.1-21.3 and a balanced reciprocal translocation between chromosomes 6 and 7 [karyotype 46,XX,t(6;7)(q23.3;q32.3)del(7)(q21.1q21.3)de novo]. We characterized the size and position of the deletion by tiling path array comparative genomic hybridization (CGH), and we mapped the translocation breakpoints on chromosomes 6 and 7 by FISH. The clinical features of this patient-severe mental retardation, short stature, microcephaly and deafness-are in accordance with previously reported patients with 7q21 deletions. Chromosome band 7q21.3 harbors a locus for split hand/split foot malformation (SHFM1), and part of this locus, including the SHFM1 candidate genes SHFM1, DLX5, and DLX6, is deleted. The absence of limb abnormalities in this patient suggests either a location of the SHFM1 causing factor distal to this deletion, or reduced penetrance of haploinsufficiency of a SHFM1 factor within the deleted interval.

Prenatal diagnosis of a 7q21.13q22.1 deletion detected using high-resolution microarray

“…1D) [3,4,5,6]. The phenotypic findings of our case were similar to previous cases and included prenatal growth retardation, facial dysplasia, and hand/foot malformations (Table 1).…”

“…Although several 7q deletion cases involving 7q21.13q22.1 have been reported, most of them involved a broader region than 7q21.13q22.1, and only a few cases were able to delineate the precise chromosomal breakpoint by high-resolution microarray analysis (Table 1) [3,4,5,6]. Since the emergence of high-resolution cytogenetic techniques in clinical diagnostics, the identification of more detailed breakpoints and the subsequent reestablishment of phenotype-genotype correlations become possible.…”

Delineation of a de novo 7q21.3q31.1 Deletion by CGH-SNP Arrays in a Girl with Multiple Congenital Anomalies Including Severe Glaucoma

“…Addition-ally, breakpoints analysis revealed that the proximal breakpoint of the present deletion lies just 88 kb downstream of the DLX5 gene. Because haploinsufficiency for DLX5 and DLX6 genes appears to be responsible for ectrodactyly [Scherer et al, 1994;van Silfhout et al, 2009], our observation indirectly confirms the exclusion of the CUX1 gene (as suggested by Bernardini et al [2008]) and potential regulatory elements (as suggested by Tzschach et al [2007]) downstream of DLX5 and ACN9 (between RP11-800O14 and D7S618) in determining such a limb defect.…”

Split hand/foot malformation due to chromosome 7q aberrations(SHFM1): additional support for functional haploinsufficiency as the causative mechanism

“…1,7 It is not known whether the same gene defect is responsible for both SHFM and deafness, or if two different genes in the SHFM1 region are involved. 11,25 In our third patient, PDD-NOS has been diagnosed. A relation between SHFM and autism has not been described previously.…”