Delineation of a complex karyotypic rearrangement by microdissection and CGH in a family affected with split foot

Weimer, Jörg; Kiechle, Marion; Wiedemann, Ute; Tönnies, Holger; Neitzel, Heidemarie; Ruhenstroth, Eberhard; Ovens-Raeder, Angela; Arnold, Norbert

doi:10.1136/jmg.37.6.442

Cited by 9 publications

(8 citation statements)

References 16 publications

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“…Analysis was performed on cases in which there was adequate clinical and radiographic information. In total, 48 SHFM1 cases were included (3–27). The breakpoints of the translocation of the patients originally described as involving 7q11.21 (6, 9) were subsequently revised to involve the SHFM1 critical region (specifically 7q21.3).…”

Section: Methodsmentioning

confidence: 99%

Discrepancies in upper and lower limb patterning in split hand foot malformation

Elliott¹,

Reed²,

Roscioli³

et al. 2005

Clinical Genetics

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Discrepancies in upper and lower limb patterning in split hand foot malformation. Split hand foot malformation (SHFM) is genetically heterogeneous with five loci mapped to date. Highly variable in presentation, it can occur as an isolated finding or with other anomalies. The genetic heterogeneity and clinical variability make genetic counselling of SHFM families challenging. By establishing genotype/phenotype correlations, one can provide insight into responsible developmental genes and help to direct mapping efforts and target genetic testing, ultimately providing more accurate information for family members. Preaxial involvement of the upper extremities was a significant discriminating limb-specific variable in our analysis of genetically mapped SHFM cases. This finding, which was originally identified through descriptive epidemiology, was subsequently confirmed by discriminant function analysis (p < 0.0001) to be a significant locus discriminator. Preaxial involvement of the upper extremities was most commonly seen at the SHFM3 locus mapped to chromosome 10q24 (OMIM 600095) and consisted of proximally placed thumbs and/or triphalangeal thumbs (TPT), preaxial polydactyly and/or absence of the first ray. These patients' feet, however, tended to show a classical central longitudinal deficiency without a significant preaxial component. This article discusses this discrepant clefting pattern between the upper and lower extremities and proposes potential mechanisms.

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Section: Methodsmentioning

confidence: 99%

Discrepancies in upper and lower limb patterning in split hand foot malformation

Elliott¹,

Reed²,

Roscioli³

et al. 2005

Clinical Genetics

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“…Chromosome 7q alterations resulting in SHFM reported thus far are summarized in Figure 3. 1,23,32 Two of our patients (1 and 2) had deletions of chromosome 7q21q22, including the genes DLX5, DLX6 and DSS1 known to have a function in SHFM1. In mice, Dlx transcription factors have been shown to have a key function in the development and morphogenesis of the limb skeleton.…”

Section: Review Of Literature and Discussionmentioning

confidence: 99%

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

et al. 2009

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We report on three patients with split hand/foot malformation type 1 (SHFM1). We detected a deletion in two patients and an inversion in the third, all involving chromosome 7q21q22. We performed conventional chromosomal analysis, array comparative genomic hybridization and fluorescence in situ hybridization. Both deletions included the known genes associated with SHFM1 (DLX5, DLX6 and DSS1), whereas in the third patient one of the inversion break points was located just centromeric to these genes. These observations confirm that haploinsufficiency due to either a simultaneous deletion of these genes or combined downregulation of gene expression due to a disruption in the region between these genes and a control element could be the cause of the syndrome. We review previously reported studies that support this hypothetical mechanism.

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“…This is partly because balanced aberrations will not be found, and partly because the sensitivity for detecting imbalances has been on the same level as routine G‐banding [detection of gains and losses of at least 10 Mb; Kallioniemi et al, 1994; Bentz et al, 1998]. Therefore, CGH has been most widely used for identifying or confirming the presence of aberrations that already have been observed by conventional G‐banding analysis [Erdel et al, 1997; Boceno et al, 1998; Levy et al, 1998; Breen et al, 1999; Weimer et al, 2000; Rigola et al, 2001].…”

Section: Introductionmentioning

confidence: 99%

Usefulness of high‐resolution comparative genomic hybridization (CGH) for detecting and characterizing constitutional chromosome abnormalities

2002

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Comparative genomic hybridization (CGH) is a technique for detection of chromosomal imbalances in a genomic DNA sample. We here report the application of the recently developed method of high-resolution CGH on DNA samples from 66 children having various degrees of delayed psychomotor development with or without clear dysmorphic features and congenital malformations. In 5 of 50 patients with apparently normal karyotypes, a deletion or duplication was revealed by CGH. Only one of these cases had a subtelomeric rearrangement. In one of seven cases with a de novo apparently balanced translocation, deletions were found. In all nine cases where the origin of a marker chromosome or additional chromosomal material was difficult to determine, CGH gave a precise identification. The following findings were from cases having a deletion or duplication as the sole chromosomal imbalance; dup(2)(p16p21), del(4)(q21q21), del(6) (q14q15), del(6)(p12p12), dup(6)(q24qter), and dup(15)(q11q13). One case had dup(9) (p11pter) combined with a very small subtelomeric deletion on 6q. In our hands, CGH is highly useful not only for identifying known chromosomal imbalances, but also for finding elusive deletions or duplications in the large group of children with developmental delay with or without congenital abnormalities. In such cases, the diagnostic yield of CGH appears to be higher than what has been reported from subtelomeric FISH screening. ß

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Delineation of a complex karyotypic rearrangement by microdissection and CGH in a family affected with split foot

Cited by 9 publications

References 16 publications

Discrepancies in upper and lower limb patterning in split hand foot malformation

Discrepancies in upper and lower limb patterning in split hand foot malformation

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

Usefulness of high‐resolution comparative genomic hybridization (CGH) for detecting and characterizing constitutional chromosome abnormalities

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