A novel mutation in TNNT3 associated with Sheldon–Hall syndrome in a Chinese family with vertical talus

Zhao, Ning; Jiang, Miao; Wang, Han; Bian, Chaoying; Li, Xuefu; Huang, Fang; Kong, Qing; Li, Jianxin

doi:10.1016/j.ejmg.2011.03.002

Cited by 21 publications

(39 citation statements)

References 6 publications

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“…Mutations in TNNT3 have been reported to cause DA [Sung et al, 2003b;Gurnett et al, 2009;Zhao et al, 2011;Beck et al, 2013]. The phenotypes were described as DA2B (Sheldon-Hall syndrome/Freeman-Sheldon variant) [Sung et al, 2003b;Zhao et al, 2011;Beck et al, 2013] and DA1 [Gurnett et al, 2009;Beck et al, 2013]. Hence, it appears that mutations in TNNT3 are likely to cause both DA1 and DA2B.…”

Section: Discussionmentioning

confidence: 99%

“…Only Zhao et al [2011] have described clinical features of 5 of their patients. We could note that brachydactyly, partial cutaneous syndactyly, broad big toes and sandal gaps are newly recognized features of this condition.…”

Section: Discussionmentioning

confidence: 99%

“…As previously defined [Bamshad et al, 1996], the boundaries between the different subtypes of DA are indistinct but have been used to aid management, counseling and investigation of the etiology of these genetically and phenotypically related conditions. Mutations in TNNT3 have been reported to cause DA [Sung et al, 2003b;Gurnett et al, 2009;Zhao et al, 2011;Beck et al, 2013]. The phenotypes were described as DA2B (Sheldon-Hall syndrome/Freeman-Sheldon variant) [Sung et al, 2003b;Zhao et al, 2011;Beck et al, 2013] and DA1 [Gurnett et al, 2009;Beck et al, 2013].…”

Section: Discussionmentioning

confidence: 99%

“…All mutations involved the amino acid position 63 (c.187C>A: p.Arg63Ser ; c.187C>T: p.Arg63Cys [Zhao et al, 2011;; c.188G>A: p.Arg63His [Sung et al, 2003b;Gurnett et al, 2009;Beck et al, 2013]). This highlights the critical role of arginine at position 63 of the troponin T3 protein.…”

Section: Discussionmentioning

confidence: 99%

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Exome Sequencing Identifies a Dominant TNNT3 Mutation in a Large Family with Distal Arthrogryposis

Daly¹,

Shah²,

O’Sullivan³

et al. 2014

Mol Syndromol

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Distal arthrogryposis (DA) is a group of rare, clinically and genetically heterogeneous disorders primarily characterized by congenital contractures of the distal limb joints without a neuromuscular disease. Mutations in at least 8 different genes have been shown to cause DA. Here, we report a 4-generation Indian family with 18 affected members presenting variable features of camptodactyly, brachydactyly, syndactyly, decreased flexion palmar creases, ulnar deviation of the hands, sandal gaps and club feet. We undertook exome sequencing of 3 distantly related affected individuals. Bioinformatics filtering revealed a known pathogenic missense mutation c.188G>A (p.Arg63His) in TNNT3 in all 3 affected individuals that segregated with the phenotype. The affected individuals exhibit significant phenotypic variability. This study demonstrates the value of exome sequencing helping to define the causative variant in genetically heterogeneous disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Exome Sequencing Identifies a Dominant TNNT3 Mutation in a Large Family with Distal Arthrogryposis

Daly¹,

Shah²,

O’Sullivan³

et al. 2014

Mol Syndromol

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“…The Sheldon-Hall type of DA also manifests significant facial features and a vertical talus; considerable non-allelic heterogeneity was demonstrated in this condition, including mutations in the gene TNNT3. [3] Thereafter, in 2011, Zhao et al [14] documented five members of three generations of a Chinese family with the Sheldon-Hall phenotype and demonstrated that they had a specific mutation in TNNT3 (c.187C>T; p.R63C). These authors suggested that bilateral vertical talus or clubfoot might be a special characteristic of this hot-spot mutation.…”

Section: Discussionmentioning

confidence: 99%

Digitotalar dysmorphism: Molecular elucidation

Vorster

Beighton

Ramesar³

2016

S Afr Med J

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Dominantly inherited digitotalar dysmorphism (DTD), which is characterised by flexion contractures of digits and 'rocker-bottom' feet due to a vertical talus, was first described in a South African family of European stock in 1972. We review the clinical manifestations and document the molecular basis for DTD in this prototype family. This family was restudied in 1995 and 2006 and biological specimens were obtained for molecular studies. Since the distal arthrogryposes (DAs) are genetically heterogeneous, an unbiased approach to mutation identification was undertaken through whole-exome next-generation sequencing of DNA from a single DTD-affected female. Venous blood specimens were obtained for DNA banking and subsequent molecular studies. Analysis of the nine genes that had previously been shown to cause DAs revealed a pathogenic mutation in exon nine of TNNT3. The presence of the p.(Arg63His) missense mutation at position 63 of TNNT3 was confirmed through direct cycle sequencing of genomic DNA in six affected family members for whom DNA had been archived.

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Spectrum of mutations that cause distal arthrogryposis types 1 and 2B

Beck

McMillin

Gildersleeve

et al. 2013

American J of Med Genetics Pt A

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The distal arthrogryposis (DA) syndromes are a group of disorders characterized by non-progressive congenital contractures of the limbs. Mutations that cause distal arthrogryposis syndromes have been reported in six genes, each of which encodes a component of the contractile apparatus of skeletal myofibers. However, these reports have usually emanated from gene discovery efforts and thus potentially bias estimates of the frequency of pathogenic mutations at each locus. We characterized the spectrum of pathogenic variants in a cohort of 153 cases of DA1 (n = 48) and DA2B (n = 105). Disease-causing mutations in 56/153 (37%) kindreds including 14/48 (29%) with DA1 and 42/105 (40%) with DA2B were distributed nearly equally across TNNI2, TNNT3, TPM2, and MYH3. In TNNI2, TNNT3, and TPM2 the same mutation caused DA1 in some families and DA2B in others. We found no significant differences among the clinical characteristics of DA by locus or between each locus and DA1 or DA2B. Collectively, the substantial overlap between phenotypic characteristics and spectrum of mutations suggest that DA1 and DA2B should be considered phenotypic extremes of the same disorder.

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A novel mutation in TNNT3 associated with Sheldon–Hall syndrome in a Chinese family with vertical talus

Cited by 21 publications

References 6 publications

Exome Sequencing Identifies a Dominant <b><i>TNNT3</i></b> Mutation in a Large Family with Distal Arthrogryposis

Exome Sequencing Identifies a Dominant <b><i>TNNT3</i></b> Mutation in a Large Family with Distal Arthrogryposis

Digitotalar dysmorphism: Molecular elucidation

Spectrum of mutations that cause distal arthrogryposis types 1 and 2B

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