Novel heterozygous frameshift mutation in distal‐less homeobox 5 underlies isolated split hand/foot malformation type 1

Ullah, Asmat; Ullah, Muhammad Farhat; Khalid, Zafar M.; Ahmad, Wasim

doi:10.1111/ped.13023

Cited by 8 publications

(6 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously, chromosomal aberrations including deletions, duplications, translocations, and inversions in 7q21.2q21.3 encompassing DLX5 , DLX6 , and DYNC1I1 have been reported in families segregating SHFM1 in an autosomal dominant pattern. Three intragenic heterozygous mutations (p.Gln186His, p.Glu39 * , and p.Ala163-Profs * 55) in the DLX5 gene causing the autosomal dominant form of SHFM1 [Sowińska-Seidler et al, 2014;Wang et al, 2014;Ullah et al, 2016] and a homozygous missense variant (p.Gln178Pro) in the same gene causing the autosomal recessive form of SHFM1 have been reported [Shamseldin et al, 2012] ( Table 1 , 2 ) . Lango et al [2014] reported that disruption of exon 15 and 17 of the DYNC1I1 gene, enhancers of DLX5/6 , caused the autosomal dominant form of SHFM1 in humans .…”

Section: Mutation Screeningmentioning

confidence: 99%

“…A homozygous mutation in the DLX5 gene was found causing SHFM1 associated with hearing loss and segregating in an autosomal recessive pattern in a family of Turkish origin [Shamseldin et al, 2012]. Recently, we reported a 4-bp duplication in the DLX5 gene causing SHFM1, segregating in an autosomal dominant manner in a family of Pakistani origin [Ullah et al, 2016]. Both DLX5 and DLX6 genes are members of the DLX gene family showing expression in the head and limbs of the developing embryo.…”

mentioning

confidence: 99%

See 1 more Smart Citation

A Novel Heterozygous Intragenic Sequence Variant in DLX6 Probably Underlies First Case of Autosomal Dominant Split-Hand/Foot Malformation Type 1

et al. 2016

Self Cite

View full text Add to dashboard Cite

Split-hand and foot malformation (SHFM; MIM 183600) is a rare human genetic limb malformation. It is characterized by missing digital rays in the hands and feet. SHFMs vary in severity from mild abnormalities affecting a single limb to acute malformations involving all 4 limbs. It is inherited, as part of both a syndromic and nonsyndromic disorder, in an autosomal recessive, autosomal dominant, and X-linked patterns. So far, 9 loci of hand and foot malformation have been mapped on human chromosomes. The present study describes a family with 2 affected individuals segregating SHFM in an autosomal dominant fashion. Sanger sequencing of the genes involved in SHFM was performed to identify the disease-causing variant. Sequence analysis revealed the first heterozygous missense variant (c.632T>A, p.Val211Glu) in the distal-less homeobox 6 (DLX6) gene, located in chromosome 7q21, causing SHFM in the present family. This study supports the evidence of DLX6 as an SHFM-causing gene.

show abstract

Section: Mutation Screeningmentioning

confidence: 99%

mentioning

confidence: 99%

A Novel Heterozygous Intragenic Sequence Variant in DLX6 Probably Underlies First Case of Autosomal Dominant Split-Hand/Foot Malformation Type 1

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Clinical examination of affected members in both families presented most of the SHFM-related features which were previously reported in families of Pakistani and other origins of the world. This included syndactyly, polydactyly, cleft hand/foot malformation, hallux valgus deformities, aplasia, hypoplasia, radial ray malformation, hypoplastic finger, and missing phalanges [Umair et al, 2018;Aziz et al, 2014;Ullah et al, 2016;Kantaputra et al, 2018;Khan et al, 2012;Ugur and Tolun 2008]. However, oligodontia/dental anomalies, brachydactyly, ectrodactyly, fusion of thumb with index finger, cardiac defects, retrognathia, thin lips, low set ears, and deafness reported previously in few SHFM cases [Ullah et al, 2016;Kantaputra et al, 2018;Khan et al, 2012;Umair et al, 2019] were not found in the present families.…”

Section: Molecular Analysismentioning

confidence: 90%

Sequence Variants in the WNT10B Underlying Non-Syndromic Split-Hand/Foot Malformation

Bilal,

Haack,

Buchert

et al. 2023

Mol Syndromol

Self Cite

View full text Add to dashboard Cite

Introduction: Split hand and foot malformation (SHFM) or ectrodactyly is a rare limb deformity characterized by median cleft of the hand and foot with impaired or missing central rays. It can occur as an isolated anomaly or in association with abnormalities of other body parts. Methods: After delineating the clinical features of two families (A–B), with non-syndromic SHFM, exome and Sanger sequencing were employed to search for the disease-causing variants. Results: Analysis of exome and Sanger sequencing data revealed two causative variants in the WNT10B gene in affected members of the two families. This included a novel missense change [c.338G>C; p.(Gly113Ala)] in family A and a previously reported frameshift variant [c.884-896delTCCAGCCCCGTCT; p.(Phe295Cysfs*87)] in family B. Conclusion: Our findings add a novel variant in WNT10B gene as the underlying cause of SHFM. The finding adds to the growing body of knowledge about the genetic basis of developmental disorders and provides valuable insights into the molecular mechanisms that regulate limb development.

show abstract

“…Mutations in DLX5 (MIM #600028) have been reported to be associated with autosomal recessive SHFM and autosomal dominant SHFM . A heterozygous missense mutation in DLX6 (MIM #600030) has been reported to be associated with SHFM (Figure ) . Dlx5 and Dlx6 genes, are known to regulate the development of the central portion of AER during early limb development.…”

Section: Shfm‐associated Genesmentioning

confidence: 99%

Genetic regulatory pathways of split‐hand/foot malformation

Kantaputra

Carlson

2018

Clinical Genetics

View full text Add to dashboard Cite

Split-hand/foot malformation (SHFM) is caused by mutations in TP63, DLX5, DLX6, FGF8, FGFR1, WNT10B, and BHLHA9. The clinical features of SHFM caused by mutations of these genes are not distinguishable. This implies that in normal situations these SHFM-associated genes share an underlying regulatory pathway that is involved in the development of the central parts of the hands and feet. The mutations in SHFM-related genes lead to dysregulation of Fgf8 in the central portion of the apical ectodermal ridge (AER) and subsequently lead to misexpression of a number of downstream target genes, failure of stratification of the AER, and thus SHFM. Syndactyly of the remaining digits is most likely the effects of dysregulation of Fgf-Bmp-Msx signaling on apoptotic cell death. Loss of digit identity in SHFM is hypothesized to be the effects of misexpression of HOX genes, abnormal SHH gradient, or the loss of balance between GLI3A and GLI3R. Disruption of canonical and non-canonical Wnt signaling is involved in the pathogenesis of SHFM. Whatever the causative genes of SHFM are, the mutations seem to lead to dysregulation of Fgf8 in AER cells of the central parts of the hands and feet and disruption of Wnt-Bmp-Fgf signaling pathways in AER.

show abstract

Novel heterozygous frameshift mutation in distal‐less homeobox 5 underlies isolated split hand/foot malformation type 1

Cited by 8 publications

References 5 publications

A Novel Heterozygous Intragenic Sequence Variant in DLX6 Probably Underlies First Case of Autosomal Dominant Split-Hand/Foot Malformation Type 1

A Novel Heterozygous Intragenic Sequence Variant in DLX6 Probably Underlies First Case of Autosomal Dominant Split-Hand/Foot Malformation Type 1

Sequence Variants in the <i>WNT10B</i> Underlying Non-Syndromic Split-Hand/Foot Malformation

Genetic regulatory pathways of split‐hand/foot malformation

Contact Info

Product

Resources

About