Homozygous sequence variants in the WNT10B gene underlie split hand/foot malformation

Ullah, Asmat; Gul, Ajab; Umair, Muhammad; Ullah, Irfan; Ahmad, Farooq; Aziz, Abdul; Wali, Abdul

doi:10.1590/1678-4685-gmb-2016-0162

Cited by 19 publications

(17 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…uruguayus , whereas it is submetacentric and significantly smaller in species of the S . catharinae clade (e.g., [103,170–179]). Cardozo et al [103] suggested that the submetacentric Pair 1 constitutes a synapomorphy of the S .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A review of the elusive bicolored iris Snouted Treefrogs (Anura: Hylidae:Scinax uruguayus group)

et al. 2019

View full text Add to dashboard Cite

The genus Scinax currently includes more than 120 species, recovered in two major clades, the S. catharinae and the S. ruber clades. The latter comprises 75 species, most of which remain unassigned to any species groups, while 12 are included in the S. rostratus and S. uruguayus groups. In this paper we present a taxonomic review of the two species currently included in the S. uruguayus group, discussing some putative phenotypic synapomorphies of this group. Although S. pinima and S. uruguayus have been considered as distinct species, this has been based on scant evidence, and several authors doubted of their distinctiveness. Our study of available specimens of S. pinima and S. uruguayus corroborates that both are valid and diagnosable species based on phenotypic evidence. Furthermore, our results show that S. pinima previously known only from its type locality, has a much widespread distribution than previously thought (including the Brazilian states of Paraná, Santa Catarina, and Rio Grande do Sul), which, added to the biological information presented here allows to suggest the removal of this species from the “Data Deficient” IUCN Red List category to “Least Concern”. Also, we describe a new species formerly reported as S. aff. pinima and S. uruguayus from NE Argentina and some localities from the Brazilian State of Rio Grande do Sul. All species are diagnosed and characterized using adult and larval morphology, osteology, vocalizations, cytogenetics, and natural history.

show abstract

Section: Discussionmentioning

confidence: 99%

“…uruguayus , and most other species of the S . ruber clade have NORs on Pair 11 (e.g., [103,172–175,179]), like many other Hylines with 2 n = 24 (see [177,178], and cites therein). The exceptions are S .…”

Section: Discussionmentioning

confidence: 99%

A review of the elusive bicolored iris Snouted Treefrogs (Anura: Hylidae:Scinax uruguayus group)

et al. 2019

View full text Add to dashboard Cite

show abstract

“…A number of families has been reported previously from Pakistan having different mutations in the WNT10B leading to SHFM phenotypes (22)(23)(24). Khan et al (9), Aziz et al (24), and Ullah et al (25), studied several Pakistani consanguineous SHFM families using linkage analysis followed by direct sequencing and identified pathogenic variants in the WNT10B gene (9,24,25). The Clinical features of affected members in these families exhibited SHFM phenotype, which is inherited in the form of autosomal recessive pattern.…”

Section: Discussionmentioning

confidence: 99%

“…Other WNT genes such as WNT3, WNT4, WNT6, WNT7A, WNT7B, WNT9B, WNT10A, and WNT16 as well as WNT10B show higher expression throughout the limb bud ectoderm in all phases of mouse limb formation with the exception of the apical ectodermal ridge where Wnt10b expression is only seen at embryonic day 11.5 (E11.5) (29,30). A few individuals were described carrying WNT10B variants exhibiting developmental tooth alterations, low bone mass or obesity but causality was not established (25,26,31,32). Such phenotypes were not observed in our patients.…”

Section: Discussionmentioning

confidence: 99%

A Novel Homozygous Nonsense Mutation p.Cys366* in the WNT10B Gene Underlying Split-Hand/Split Foot Malformation in a Consanguineous Pakistani Family

et al. 2020

Self Cite

View full text Add to dashboard Cite

Split hand/split foot malformation (SHFM) or ectrodactyly is characterized by a deep median cleft of the hand or foot, hypoplasia or aplasia of the metacarpals, metatarsals, and phalanges. It is a clinically and genetically heterogeneous group of limb malformations. This study aimed to identify the pathogenic variant in a consanguineous Pakistani family with autosomal recessive SHFM. Peripheral blood samples were obtained, DNA was extracted, WNT10B coding and noncoding regions were PCR amplified and Sanger sequencing was performed using workflow suggested by Thermo Fisher Scientific. A novel homozygous nonsense variant (c.1098C>A; p.Cys366 *) was identified in the WNT10B gene in the index patients, which probably explains SHFM type 6 in this family in comparison with similar data from the literature.

show abstract

“…It is categorized into two types: the postaxial type A (PAPA; well-developed extra digit) and the postaxial type B (PAPB; hypoplastic rudimentary extra digit or a skin tag or appears as a small protuberance). Polydactyly may occur as a non syndromic form (isolated) or in association with other severe abnormalities (syndromic form) such as Bardet-Biedl syn drome, split hand/foot malformation, syndactyly, and Ellis-Van Creveld syndrome, respectively (Khan et al, 2012;Ullah, Gul, et al, 2018;Ullah, Khalid, et al, 2018;Ullah, Umair, et al, 2017Umair, Ahmad, Bilal, & Abbas, 2018Umair, Ahmad, Bilal, Ahmad, & Alfadhel, 2018;Umair, Seidel, et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Exome sequencing revealed a novel loss‐of‐function variant in the GLI3 transcriptional activator 2 domain underlies nonsyndromic postaxial polydactyly

Umair

Wasif

Albalawi

et al. 2019

Molec Gen & Gen Med

Self Cite

View full text Add to dashboard Cite

Background Polydactyly is a common genetic limb deformity characterized by the presence of extra fingers or toes. This anomaly may occur in isolation (nonsyndromic) or as part of a syndrome. The disease is broadly divided into preaxial polydactyly (PPD; duplication of thumb), mesoaxial polydactyly (complex polydactyly), and postaxial polydactyly (PAP: duplication of the fifth finger). The extra digits may be present in one or both the limbs. Heterozygous variants in the GLI3 , ZRS / SHH , and PITX1 have been associated with autosomal dominant polydactyly, while homozygous variants in the ZNF141 , IQCE , GLI1 , and FAM92A have been associated with autosomal recessive polydactyly. Pathogenic mutations in the GLI3 gene (glioma‐associated oncogene family zinc finger 3) have been associated with both nonsyndromic and syndromic polydactyly. Methods Here, we report an extended five generation kindred having 12 affected individuals exhibiting nonsyndromic postaxial polydactyly type A condition. Whole‐exome sequencing followed by variant prioritization, bioinformatic studies, Sanger validation, and segregation analysis was performed. Results Using exome sequencing in the three affected individuals, we identified a novel heterozygous frameshift variant (c.3567_3568insG; p.Ala1190Glyfs*57) in the transcriptional activator (TA2) domain of the GLI3 encoding gene. Conclusion To the best of our knowledge, the present study reports on the first familial case of nonsyndromic postaxial polydactyly due to the GLI3 variant in Pakistani population. Our study also demonstrated the important role of GLI3 in causing nonsyndromic postaxial polydactyly.

show abstract

Homozygous sequence variants in the WNT10B gene underlie split hand/foot malformation

Cited by 19 publications

References 26 publications

A review of the elusive bicolored iris Snouted Treefrogs (Anura: Hylidae:Scinax uruguayus group)

A review of the elusive bicolored iris Snouted Treefrogs (Anura: Hylidae:Scinax uruguayus group)

A Novel Homozygous Nonsense Mutation p.Cys366* in the WNT10B Gene Underlying Split-Hand/Split Foot Malformation in a Consanguineous Pakistani Family

Exome sequencing revealed a novel loss‐of‐function variant in the GLI3 transcriptional activator 2 domain underlies nonsyndromic postaxial polydactyly

Contact Info

Product

Resources

About