Advances in the Molecular Genetics of Non-syndromic Syndactyly

Deng, Hao; Tan, Ting

doi:10.2174/1389202916666150317233103

Cited by 14 publications

(4 citation statements)

References 94 publications

(172 reference statements)

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“…Based on the anatomic position of the additional digits, polydactyly can be classified into preaxial polydactyly (PPD), postaxial polydactyly and central polydactyly [3]. Previous pathological researches have shown that most of the PPD abnormal cases follow an autosomal dominant inheritance pattern and a few express an autosomal recessive pattern of inheritance [4]. In addition to high incidence in humans, there is high morbidity rate in pigs, cats, chickens and other vertebrates [5].…”

Section: Introductionmentioning

confidence: 99%

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Whole genome resequencing reveals an association of ABCC4 variants with preaxial polydactyly in pigs

Khederzadeh

Adeola

et al. 2020

BMC Genomics

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Background: Polydactyly is one of the most common congenital limb dysplasia in many animal species. Although preaxial polydactyly (PPD) has been comprehensively studied in humans as a common abnormality, the genetic variations in other animal species have not been fully understood. Herein, we focused on the pig, as an even-toed ungulate mammal model with its unique advantages in medical and genetic researches, two PPD families consisting of four affected and 20 normal individuals were sequenced. Results: Our results showed that the PPD in the sampled pigs were not related to previously reported variants. A strong association was identified at ABCC4 and it encodes a transmembrane protein involved in ciliogenesis. We found that the affected and normal individuals were highly differentiated at ABCC4, and all the PPD individuals shared long haplotype stretches as compared with the unaffected individuals. A highly differentiated missense mutation (I85T) in ABCC4 was observed at a residue from a transmembrane domain highly conserved among a variety of organisms. Conclusions: This study reports ABCC4 as a new candidate gene and identifies a missense mutation for PPD in pigs. Our results illustrate a putative role of ciliogenesis process in PPD, coinciding with an earlier observation of ciliogenesis abnormality resulting in pseudo-thumb development in pandas. These results expand our knowledge on the genetic variations underlying PPD in animals.

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Section: Introductionmentioning

confidence: 99%

“…[31], TWIST1 [32], PITX1 [33] etc. and reviewed in Malik et al [2] and Deng et al [4]. Among all of these identified candidate genes, majority of them are involved in the SHH signaling pathway or ciliogenesis process.…”

Section: Introductionmentioning

confidence: 99%

Whole genome resequencing reveals an association of ABCC4 variants with preaxial polydactyly in pigs

Khederzadeh

Adeola

et al. 2020

BMC Genomics

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“…Webbing of adjacent digits with or without bony fusion is termed as syndactyly and it is a common hereditary limb anomaly. It can occur either as an isolated malformation or as a component of a syndromic diagnosis and more than 300 associated syndromes have been identified [ 18 ]. Oligosyndactyly is one of the syndactyly phenotypes and it is a frequent feature in several syndromes, namely, CLS syndrome, fibular aplasia, tibial campomelia and oligosyndactyly (FATCO) syndrome, fibular hemimelia (FH), Cornelia de Lange (CdL) syndrome and chromosome 2q35 duplication syndrome.…”

Section: Discussionmentioning

confidence: 99%

Van Wyk-Grumbach syndrome and oligosyndactyly in a 6-year-old girl: a case report

et al. 2020

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Background Van Wyk-Grumbach syndrome refers to the development of isosexual precocious pseudopuberty and multicystic enlarged ovaries in the presence of hypothyroidism and delayed bone age. It is a rare presentation of untreated hypothyroidism. The prepubertal response in Van Wyk-Grumbach syndrome is always isosexual and mediated by very high thyroid-stimulating hormone levels acting through the follicle-stimulating hormone receptors inducing a follicle-stimulating hormonal effect. Early recognition and thyroid hormone replacement can completely regress precocious puberty and ovarian enlargement, while improving the final height achievement. Oligosyndactly is a congenital bony abnormality and can manifest either as an isolated malformation or as a component of a syndromic diagnosis. However, development of hypothyroidism in children with this peculiar bony deformity has rarely been described in the medical literature, with the exception of Cenani-Lenz Syndactyly syndrome. Case presentation We report the case of a 6-year-old Sri Lankan girl who presented with a 2-day history of vaginal bleeding and exertional dyspnea. She had marked short stature (well below −3 standard deviations) with an upper segment to lower segment ratio of 1.47. This girl had isolated breast development of Tanner stage 2. She was diagnosed to have acquired hypothyroidism secondary to autoimmune thyroiditis and also had macrocytic anemia, pericardial effusion, gonadotropin-releasing hormone-independent precocious puberty with radiological evidence of pubertal changes in the uterus, and multicystic ovaries. Interestingly, she also had post-axial oligosyndactyly in both feet and right-sided clubfoot. The diagnosis of Van Wyk-Grumbach syndrome was made based on the clinical and laboratory features. Her symptoms were successfully managed with L-thyroxine therapy. Conclusions Acquired hypothyroidism is a relatively common endocrine disorder among children and early recognition is important to prevent serious complications like Van Wyk-Grumbach syndrome. Sexual precocity with delayed bone age and stunting should direct our minds toward this unique diagnosis. It is always necessary to identify the other associated anomalies in addition to the primary diagnosis since these features may direct to a syndromic diagnosis.

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“…Nonsyndromic syndactyly manifests itself as 9 distinct types; at least 11 loci and 8 relevant genes have been identified 27 (Fig. 1 ).…”

Section: Nonsyndromic Dactylies: Phenotypes and Geneticsmentioning

confidence: 99%

Genetic Overview of Syndactyly and Polydactyly

Ahmed

Akbari

Emami

et al. 2017

Plastic and Reconstructive Surgery - Global Open

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Summary:Syndactyly and polydactyly—respectively characterized by fused and supernumerary digits—are among the most common congenital limb malformations, with syndactyly presenting at an estimated incidence of 1 in 2,000–3,000 live births and polydactyly at a frequency of 1 in approximately 700–1,000 live births. Despite their relatively regular manifestation in the clinic, the etiologies of syndactyly and polydactyly remain poorly understood because of their phenotypic and genetic diversity. Further, even though concrete knowledge of genotypic links has been established for some variants of syndactyly and polydactyly, there appears to be no single comprehensive published summary of all syndromic and nonsyndromic syndactyly and polydactyly presentations, and there is decidedly no resource that maps all syndromic and nonsyndromic syndactylies and polydactylies to their genetic bases. This gap in the literature problematizes comprehensive carrier screening and prenatal diagnosis and complicates novel diagnostic attempts. This review thus attempts to collect all that is known about the genetic bases of syndromic and nonsyndromic syndactylies and polydactylies, as well as to highlight the dactyly manifestations for which no genetic bases are as yet known. Then, having established a summation of existing and missing knowledge, this work briefly outlines the diagnostic techniques that a genetics-reinforced understanding of syndactyly and polydactyly could inform.

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Advances in the Molecular Genetics of Non-syndromic Syndactyly

Cited by 14 publications

References 94 publications

Whole genome resequencing reveals an association of ABCC4 variants with preaxial polydactyly in pigs

Whole genome resequencing reveals an association of ABCC4 variants with preaxial polydactyly in pigs

Van Wyk-Grumbach syndrome and oligosyndactyly in a 6-year-old girl: a case report

Genetic Overview of Syndactyly and Polydactyly

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