Review of Literature: Genes Related to Postaxial Polydactyly

Verma, Prashant Kumar; El-Harouni, Ashraf A.

doi:10.3389/fped.2015.00008

Cited by 23 publications

(25 citation statements)

References 99 publications

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“…GLI3 mutations (ranging from point mutations to large rearrangements) are known to be associated with several syndromes/conditions in which polydactyly is a feature ( Table 1) (1)(2)(3)(4)(5)(6)(7)(8)(9).…”

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confidence: 99%

GLI3‐related polydactyly: a review

et al. 2017

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GLI3 mutations are known to be associated with nine syndromes/conditions in which polydactyly is a feature. In this review, the embryology, pathogenesis, and animal models of GLI3-related polydactyly are discussed first. This is followed by a detailed review of the genotype-phenotype correlations. Based on our review of the literature and our clinical experiences, we recommend viewing GLI3-related syndromes/conditions as four separate entities; each characterized by a specific pattern of polydactyly. These four entities are: the preaxial polydactyly type IV-Greig-acrocallosal spectrum, postaxial polydactyly types A/B, Pallister-Hall syndrome (PHS), and oral-facial-digital overlap syndrome. We also provide illustrative clinical examples from our practice including a family with a novel GLI3 mutation causing PHS. The review also introduces the term 'Forme Fruste' preaxial polydactyly and gives several conclusions/recommendations including the recommendation to revise the current criteria for the clinical diagnosis of PHS.

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confidence: 99%

GLI3‐related polydactyly: a review

et al. 2017

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“…(40,41) Impaired ciliogenesis is often associated with polydactyly disorders, including PAP. (3) We illustrate this as well as cilium-associated processes are highly and significantly overrepresented in PAP in an overrepresentation analysis. (13) FAM92A is also involved in these shared underlying pathological processes.…”

Section: Discussionmentioning

confidence: 78%

“…As mentioned above, polydactyly disorders are associated with impaired ciliogenesis. (3) However, the primary cilium has been implicated in the growth of neoplasms as well, such as osteomas, as it is crucial in the development, growth, patterning, and orientation of cells and tissues. (42) Defective cilia can lead to a disorganization of vital signaling during cell replication and the cell fate decisions that can contribute to the growth of neoplasms early in life.…”

Section: Discussionmentioning

confidence: 99%

“…(2) Nonsyndromic PAP can be broadly divided into two types: PAPA, with fully developed extra digits, and PAPB, showing incompletely developed extra digits (pedunculated postminimus). (3) …”

Section: Introductionmentioning

confidence: 99%

“…(13) Genes associated with syndromic or nonsyndromic PAP can be classified under ciliopathies (ie, genes related to cilia biogenesis, structure, and functions) and nonciliopathies. (3) Known PAP syndromic ciliopathies include Meckel and Bardet-Biedl syndromes. (3) GLI3 and IQCE both regulate sonic hedgehog (SHH) signaling, (14,15) which localizes to or shuttles through the primary cilium.…”

Section: Introductionmentioning

confidence: 99%

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FAM92A Underlies Nonsyndromic Postaxial Polydactyly in Humans and an Abnormal Limb and Digit Skeletal Phenotype in Mice

Schrauwen

Giese

Aziz

et al. 2018

Journal of Bone and Mineral Research

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Polydactyly is a common congenital anomaly of the hand and foot. Postaxial polydactyly (PAP) is characterized by one or more posterior or postaxial digits. In a Pakistani family with autosomal recessive nonsyndromic postaxial polydactyly type A (PAPA), we performed genomewide genotyping, linkage analysis, and exome and Sanger sequencing. Exome sequencing revealed a homozygous nonsense variant (c.478C>T, p.[Arg160*]) in the FAM92A gene within the mapped region on 8q21.13-q24.12 that segregated with the PAPA phenotype. We found that FAM92A is expressed in the developing mouse limb and E11.5 limb bud including the progress zone and the apical ectodermal ridge, where it strongly localizes at the cilia level, suggesting an important role in limb patterning. The identified variant leads to a loss of the FAM92A/Chibby1 complex that is crucial for ciliogenesis and impairs the recruitment and the colocalization of FAM92A with Chibby1 at the base of the cilia. In addition, we show that Fam92a−/− homozygous mice also exhibit an abnormal digit morphology, including metatarsal osteomas and polysyndactyly, in addition to distinct abnormalities on the deltoid tuberosity of their humeri. In conclusion, we present a new nonsyndromic PAPA ciliopathy due to a loss-of-function variant in FAM92A.

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Hypomorphic MKS1 mutation in a Pakistani family with mild Joubert syndrome and atypical features: Expanding the phenotypic spectrum of MKS1‐related ciliopathies

Ullah

Khan

Ullah

et al. 2016

American J of Med Genetics Pt A

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Postaxial polydactyly (PAP) is one of the most common congenital malformations observed in the general population. However, it can also occur as part of a syndrome. Unbiased genetic screening techniques such as exome sequencing are highly appropriate methods to provide a molecular diagnosis in patients with polydactyly due to the large number of mutated genes associated with it. The present study describes a consanguineous family of Pakistani origin with PAP, speech impairment, hearing impairment of variable degree, and proportionate short stature with no prominent intellectual disability or ophthalmological abnormalities. One affected individual of the family was subjected to exome sequencing which resulted in the identification of four homozygous variants including an in-frame deletion (c.1115_1117delCCT; p.(Ser372del) in MKS1, which was later shown to be the only variant segregating with the phenotype. In silico predictions supported the potential pathogenicity of the identified mutation. Additional clinical tests and MRI features of a patient in the family showed a molar tooth sign, which is a hallmark of Joubert syndrome. In conclusion, we have described a pathogenic variant in the MKS1 resulting in a mild Joubert syndrome phenotype, which broadens the spectrum of mutations in the MKS1. © 2016 Wiley Periodicals, Inc.

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Review of Literature: Genes Related to Postaxial Polydactyly

Cited by 23 publications

References 99 publications

GLI3‐related polydactyly: a review

GLI3‐related polydactyly: a review

FAM92A Underlies Nonsyndromic Postaxial Polydactyly in Humans and an Abnormal Limb and Digit Skeletal Phenotype in Mice

Hypomorphic MKS1 mutation in a Pakistani family with mild Joubert syndrome and atypical features: Expanding the phenotypic spectrum of MKS1‐related ciliopathies

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