Holoprosencephaly, hypertelorism, and ectrodactyly in a boy with an apparently balanced de novo t(2;4)(q14.2;q35)

Corona‐Rivera, Alfredo; Corona‐Rivera, Jorge Román; Bobadilla‐Morales, Lucina; Cobián, Teresa Arcelia García; Corona-Rivera, E.

doi:10.1002/(sici)1096-8628(20000228)90:5<423::aid-ajmg12>3.0.co;2-k

Cited by 17 publications

(22 citation statements)

References 11 publications

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“…An apparently balanced de novo translocation with a breakpoint at 2q14.2 was identified in a patient with SHFM and holoprosencephaly (HPE) [Corona-Rivera et al, 2000]. A patient with SHFLD was later found to have a balanced translocation that also involved 2q14.2 [Babbs et al, 2007].…”

Section: Balanced/unbalanced Chromosome Rearrangementsmentioning

confidence: 99%

Clinical, genetic, and molecular aspects of split‐hand/foot malformation: An update

Gurrieri

Everman

2013

American J of Med Genetics Pt A

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We here provide an update on the clinical, genetic, and molecular aspects of split-hand/foot malformation (SHFM). This rare condition, affecting 1 in 8,500-25,000 newborns, is extremely complex because of its variability in clinical presentation, irregularities in its inheritance pattern, and the heterogeneity of molecular genetic alterations that can be found in affected individuals. Both syndromal and nonsyndromal forms are reviewed and the major molecular genetic alterations thus far reported in association with SHFM are discussed. This updated overview should be helpful for clinicians in their efforts to make an appropriate clinical and genetic diagnosis, provide an accurate recurrence risk assessment, and formulate a management plan.

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Section: Balanced/unbalanced Chromosome Rearrangementsmentioning

confidence: 99%

Clinical, genetic, and molecular aspects of split‐hand/foot malformation: An update

Gurrieri

Everman

2013

American J of Med Genetics Pt A

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“…8 Comparative mapping of the two chromosomes 2 breakpoints BAC clones were selected on the basis of the cytogenetically established chromosome breakpoint regions ( Figure 2a and b) using the ensemble database. These were hybridized against metaphase chromosome spreads of the two probands.…”

Section: Probands and Cytogenetic Analysismentioning

confidence: 99%

“…As an example, a holoprosencephaly, hypertelorism and ectrodactyly syndrome (HHES), considered as an independent clinical entity, was reported to be associated with an apparently balanced de novo translocation [t(2;4) (q14.2;q35)] in a Mexican patient. 8 In addition to this case, an association of ectrodactyly with holoprosencephaly has been reported in six additional probands (reviewed by König et al 9 ).…”

Section: Introductionmentioning

confidence: 99%

Characterization of two ectrodactyly-associated translocation breakpoints separated by 2.5 Mb on chromosome 2q14.1–q14.2

et al. 2009

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Split hand-split foot malformation or ectrodactyly is a heterogeneous congenital defect of digit formation. The aim of this study is the mapping of the breakpoints and a detailed molecular characterization of the candidate genes for an isolated and syndromic form of ectrodactyly, both associated with de novo apparently balanced chromosome translocations involving the same chromosome 2 band, [t(2;11)(q14.2;q14.2)] and [t(2;4)(q14.1;q35)], respectively. Breakpoints were mapped by fluorescence in situ hybridization using bacterial artificial chromosome clones. Where possible, these breakpoints were further delimited. Candidate genes were screened for pathogenic mutations and the expression levels of two of them analysed. The isolated bilateral split foot malformation-associated chromosome 2 breakpoint was localized at 120.9 Mb, between the two main candidate genes, encoding GLI-Kruppel family member GLI2 and inhibin-bB. The second breakpoint associated with holoprosencephaly, hypertelorism and ectrodactyly syndrome was mapped 2.5 Mb proximal at 118.4 Mb and the candidate genes identified from this region were the insulin-induced protein 2 and the homeobox protein engrailed-1. No clear pathogenic mutations were identified in any of these genes. The breakpoint between INHBB and GLI2 coincides with a previously identified translocation breakpoint associated with ectrodactyly. We propose a mechanism by which translocations in the 2q14.1 -q14.2 region disrupt the specific arrangement of long-range regulatory elements that control the tight quantitative spatiotemporal expression of one or more genes from the breakpoint region.

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“…Initially, two pieces of evidence suggested that the 2q14.2 breakpoint might signal a locus for SHFLD. First, the report of a patient with a t(2;4)(q14.2;q35) translocation associated with holoprosencephaly and ectrodactyly suggested a common aetiology (Corona-Rivera et al 2000). Second, deletions of the short arm of chromosome 18 are relatively frequent and are not associated with limb abnormalities while conWrmed deletions of 2q14.2 are extremely rare (Schinzel 2001).…”

Section: Introductionmentioning

confidence: 64%

A new locus for split hand/foot malformation with long bone deficiency (SHFLD) at 2q14.2 identified from a chromosome translocation

et al. 2007

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Split hand/foot malformation (SHFM) with long bone deWciency (SHFLD) is a distinct entity in the spectrum of ectrodactylous limb malformations characterised by associated tibial a/hypoplasia. Pedigrees with multiple individuals aVected by SHFLD often include nonpenetrant intermediate relatives, making genetic mapping diYcult. Here we report a sporadic patient with SHFLD who carries a de novo chromosomal translocation t(2;18)(q14.2;p11.2). Characterisation of the breakpoints revealed that neither disrupts any known gene; however, the chromosome 2 breakpoint lies between GLI2 and INHBB, two genes known to be involved in limb development. To investigate whether mutation of a gene in proximity to the chromosome 2 breakpoint underlies the SHFLD, we sought independent evidence of mutations in GLI2, INHBB and two other genes (RALB and FLJ14816) in 44 unrelated patients with SHFM, SHFLD or isolated long bone deWciency. No convincing pathogenic mutations were found, raising the possibility that a long-range cis acting regulatory element may be disrupted by this translocation. The previous description of a translocation with a 2q14.2 breakpoint associated with ectrodactyly, and the mapping of the ectrodactylous Dominant hemimelia mouse mutation to a region of homologous synteny, suggests that 2q14.2 represents a novel locus for SHFLD.

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Holoprosencephaly, hypertelorism, and ectrodactyly in a boy with an apparently balanced de novo t(2;4)(q14.2;q35)

Cited by 17 publications

References 11 publications

Clinical, genetic, and molecular aspects of split‐hand/foot malformation: An update

Clinical, genetic, and molecular aspects of split‐hand/foot malformation: An update

Characterization of two ectrodactyly-associated translocation breakpoints separated by 2.5 Mb on chromosome 2q14.1–q14.2

A new locus for split hand/foot malformation with long bone deficiency (SHFLD) at 2q14.2 identified from a chromosome translocation

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