A novel type of autosomal recessive syndactyly: Clinical and molecular studies in a family of Pakistani origin

Malik, Sajid; Arshad, Muhammad Imran; Aminuddin, Muhammad; Oeffner, Frank; Dempfle, Astrid; Haque, Sayedul; Koch, Manuela C.; Ahmad, Wasim; Grzeschik, Karl‐Heinz

doi:10.1002/ajmg.a.20555

Cited by 18 publications

(22 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, the limb phenotype in the absence of Epfn is comparable to the recently identified human mesoaxial synostotic syndactyly (MSSD, type IX syndactyly) (Malik et al, 2004; 2005) although the specific digits affected differs between human and mouse. This type of syndactyly is characterized by the mesoaxial reduction of fingers due to bony fusion of the third and fourth metacarpals bearing single phalanges.…”

Section: Discussionsupporting

confidence: 62%

Role of Epiprofin, a zinc-finger transcription factor, in limb development

Talamillo

Delgado

Nakamura

et al. 2010

Developmental Biology

View full text Add to dashboard Cite

The formation and maintenance of the apical ectodermal ridge (AER) is critical for the outgrowth and patterning of the vertebrate limb. In the present work, we have investigated the role of Epiprofin (Epfn/Sp6), a member of the SP/KLF transcription factor family that is expressed in the limb ectoderm and the AER, during limb development. Epfn mutant mice have a defective autopod that shows mesoaxial syndactyly in the forelimb and synostosis (bony fusion) in the hindlimb and partial bidorsal digital tips. Epfn mutants also show a defect in the maturation of the AER that appears flat and broad, with a double ridge phenotype. By genetic analysis, we also show that Epfn is controlled by WNT/b-CATENIN signaling in the limb ectoderm. Since the less severe phenotypes of the conditional removal of b-catenin in the limb ectoderm strongly resemble the limb phenotype of Epfn mutants, we propose that EPFN very likely functions as a modulator of WNT signaling in the limb ectoderm.

show abstract

Section: Discussionsupporting

confidence: 62%

Role of Epiprofin, a zinc-finger transcription factor, in limb development

Talamillo

Delgado

Nakamura

et al. 2010

Developmental Biology

View full text Add to dashboard Cite

show abstract

“…Malik et al, [124] found similar findings in another family, with an autosomal recessive trait, and ruled out genome candidates at 2q34-q36, 2q31, and 6q22-q23. The previous family had had HOXD13 and the genome associated with 2q31 disproved as causative by Percin et al, Merging the two families into one study has revealed a likelihood of a causal gene being mapped to chromosome 17p13.3 [125].…”

Section: Syndactyly: the Genetic Search And A Problem For Clinical CLmentioning

confidence: 65%

The Epidemiology, Genetics and Future Management of Syndactyly

Jordan¹,

Hindocha²,

Dhital³

et al. 2012

TOORTHJ

View full text Add to dashboard Cite

Syndactyly is a condition well documented in current literature due to it being the most common congenital hand defect, with a large aesthetic and functional significance.There are currently nine types of phenotypically diverse non-syndromic syndactyly, an increase since the original classification by Temtamy and McKusick(1978). Non-syndromic syndactyly is inherited as an autosomal dominant trait, although the more severe presenting types and sub types appear to have autosomal recessive and in some cases X-linked hereditary.Gene research has found that these phenotypes appear to not only be one gene specific, although having individual localised loci, but dependant on a wide range of genes and subsequent signalling pathways involved in limb formation. The principal genes so far defined to be involved in congenital syndactyly concern mainly the Zone of Polarizing Activity and Shh pathway.Research into the individual phenotypes appears to complicate classification as new genes are found both linked, and not linked, to each malformation. Consequently anatomical, phenotypical and genotypical classifications can be used, but are variable in significance, depending on the audience.Currently, management is surgical, with a technique unchanged for several decades, although future development will hopefully bring alternatives in both earlier diagnosis and gene manipulation for therapy.

show abstract

“…Malik et al (2005) described the mapping of a locus for an autosomal recessive form of mesoaxial synostotic syndactyly, MSSD-type IX with phalangeal reduction to chromosome region 17p13.3. (Malik et al 2004(Malik et al , 2005. The SHFLD locus mapped by us is fully enclosed in the MSSDtype IX syndactyly locus.…”

Section: Resultsmentioning

confidence: 99%

A novel locus for split-hand/foot malformation associated with tibial hemimelia (SHFLD syndrome) maps to chromosome region 17p13.1–17p13.3

et al. 2008

View full text Add to dashboard Cite

Split-hand/foot malformation (SHFM) associated with aplasia of long bones, SHFLD syndrome or Tibial hemimelia-ectrodactyly syndrome is a rare condition with autosomal dominant inheritance, reduced penetrance and an incidence estimated to be about 1 in 1,000,000 liveborns. To date, three chromosomal regions have been reported as strong candidates for harboring SHFLD syndrome genes: 1q42.2-q43, 6q14.1 and 2q14.2. We characterized the phenotype of nine affected individuals from a large family with the aim of mapping the causative gene. Among the nine affected patients, four had only SHFM of the hands and no tibial defects, three had both defects and two had only unilateral tibial hemimelia. In keeping with previous publications of this and other families, there was clear evidence of both variable expression and incomplete penetrance, the latter bearing hallmarks of anticipation. Segregation analysis and multipoint Lod scores calculations (maximum Lod score of 5.03 using the LINKMAP software) using all potentially informative family members, both affected and unaffected, identified the chromosomal region 17p13.1-17p13.3 as the best and only candidate for harboring a novel mutated gene responsible for the syndrome in this family. The candidate gene CRK located within this region was sequenced but no pathogenic mutation was detected.

show abstract

A novel type of autosomal recessive syndactyly: Clinical and molecular studies in a family of Pakistani origin

Cited by 18 publications

References 17 publications

Role of Epiprofin, a zinc-finger transcription factor, in limb development

Role of Epiprofin, a zinc-finger transcription factor, in limb development

The Epidemiology, Genetics and Future Management of Syndactyly

A novel locus for split-hand/foot malformation associated with tibial hemimelia (SHFLD syndrome) maps to chromosome region 17p13.1–17p13.3

Contact Info

Product

Resources

About