Schmid Type Metaphyseal Chondrodysplasia with a Novel COL10A1 Mutation

Goyal, Manisha; Gupta, Ashok; Choudhary, Anita; Bhandari, Anu

doi:10.1007/s12098-018-2791-0

Cited by 10 publications

(11 citation statements)

References 8 publications

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“…Following the initial report of the COL10A1 gene mutation in SMCD [Mäkitie et al, 2005], at least 48 different heterozygous COL10A1 mutations have been reported in families with SMCD of different ethnic origin [Higuchi et al, 2016]. To date, the majority of mutations occur within the C-terminal NC1 domain [Mäkitie et al, 2005;Park et al, 2015;Higuchi et al, 2016;Goyal et al, 2018], which contains motifs that promote trimerization of the α1(X) chains and subsequent formation of the triple helix to yield stable collagen X molecules [Higuchi et al, 2016;Goyal et al, 2018]. Missense, nonsense, and frameshift mutations have been reported in the NC1 domain, and in 53% of the cases, premature termination codons resulting from nonsense and frameshift mutations have been reported.…”

Section: Discussionmentioning

confidence: 99%

“…Several frameshift mutations have been reported in the COL10A1 gene and affected patients present with a similar phenotype as seen in our case, including short stature, waddling gate, metaphyseal irregularities, and coxa vara. However, the phenotype severity and others findings such as hyperlordosis showed both inter-and intrafamilial variability [Mäikitie et al, 2005;Woelfle et al, 2011;Park et al, 2015;Higuchi et al, 2016;Goyal et al, 2018].…”

Section: Discussionmentioning

confidence: 99%

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A Venezuelan Case of Schmid-Type Metaphyseal Chondrodysplasia with a Novel Mutation in COL10A1

et al. 2019

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Schmid-type metaphyseal chondrodysplasia (MIM 156500) is an uncommon autosomal dominant skeletal dysplasia caused by heterozygous mutations in the COL10A1 gene (MIM 120110) encoding the α1(X) chains of type X collagen. We report an 8-year-old girl with waddling gait, short stature, mild dorsal scoliosis, coxa vara, short lower limbs, bowing of the femurs, genu varum, and metaphyseal fraying and splaying, who is a carrier of a novel heterozygous 2-bp (c.1894_1895dupTA; p.Leu633Thrfs*45) duplication in exon 3 of the COL10A1 gene.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A Venezuelan Case of Schmid-Type Metaphyseal Chondrodysplasia with a Novel Mutation in COL10A1

et al. 2019

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“…All of the identified mutation sites of COL10A1 associated with MCDS, including mutations in the present study, are located in the NC1 domain [4,8,12,22,23,24,25,26,27,28], except for two missense mutations in the signal peptide and one in the triple helical domain.…”

Section: Discussionmentioning

confidence: 50%

Identification of two novel COL10A1 heterozygous mutations in two Chinese pedigrees with Schmid-type metaphyseal chondrodysplasia

Kong

Shi

Wang

et al. 2019

Preprint

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Background: Schmid-type metaphyseal chondrodysplasia (MCDS) is an autosomal dominant disorder caused by COL10A1 mutations, which is characterized by short stature, waddling gait, coxa vara and bowing of the long bones. However, descriptions of the expressivity of MCDS are rare. Methods: Two probands and available family members affected with MCDS were subjected to clinical and radiological examination. Genomic DNA of all affected individuals was subjected to whole-exome sequencing, and candidate mutations were verified by Sanger sequencing in all available family members and in 250 healthy donors. A spatial model of the type X collagen (α1) C-terminal noncollagenous (NC1) domain was further constructed. Results: We found that the phenotype of affected family members exhibited incomplete dominance. Mutation analysis indicated that there were two novel heterozygous missense mutations, [c.1765T>A (p.Phe589Ile)] and [c.1846A>G (p.Lys616Glu)] in the COL10A1 gene in family 1 and 2, respectively. The two novel substitution sites were highly conserved and the mutations were predicted to be deleterious by in silico analysis. Furthermore, protein modeling revealed that the two substitutions were located in the NC1 domain of collagen X (α1), which potentially impacted the trimerization of collagen X (α1) and combination with molecules in the pericellular matrix. Conclusion: Two novel mutations were identified in the present study, which will facilitate diagnosis of MCDS and further expand the spectrum of the COL10A1 mutations associated with MCDS patients. In addition, our research revealed the phenomenon of incomplete dominance in MCDS.

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“…To the best of our knowledge, this is the first report of MDSC associated with factor VII deficiency worldwide. There have been reports of MDSC from other regions, including India (three-year old girl), Venezuela (eight-year-old girl), and Japan (three-year-old boy) [1,6,10]. A cohort study done by Makitie et al included 10 patients with confirmed MDSC, who were subsequently followed over time [11].…”

Section: Discussionmentioning

confidence: 99%

“…Metaphyseal chondrodysplasia, Schmid type (MDSC) is a rare autosomal dominant condition caused by a mutation in the COL10A1 gene [1]. It manifests in early childhood and results in a wide range of skeletal deformities.…”

Section: Introductionmentioning

confidence: 99%

A Novel Presentation of Metaphyseal Chondrodysplasia, Schmid Type with Factor VII Deficiency

Ahmed¹,

Nasir²,

Hashmi³

et al. 2020

Cureus

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Metaphyseal chondrodysplasia, Schmid type (MDSC) is a rare inherited autosomal disorder with characteristic skeletal deformities striking on radiological imaging, which includes metaphyseal cupping and fraying. Physical examination reveals short stature in early childhood, frontoparietal bossing, rachitic rosary, genu varum and valgum, and coxa vara usually. We believe that the constellation of clinical and radiographic findings of MDSC might look similar to vitamin D resistant rickets; hence, genetic analysis is needed to overcome diagnostic challenges faced by physicians to avoid unnecessary vitamin D supplementation in individuals. We report the first case of MDSC with a coexisting factor VII deficiency in an eightyear-old boy.

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Schmid Type Metaphyseal Chondrodysplasia with a Novel COL10A1 Mutation

Cited by 10 publications

References 8 publications

A Venezuelan Case of Schmid-Type Metaphyseal Chondrodysplasia with a Novel Mutation in COL10A1

A Venezuelan Case of Schmid-Type Metaphyseal Chondrodysplasia with a Novel Mutation in COL10A1

Identification of two novel COL10A1 heterozygous mutations in two Chinese pedigrees with Schmid-type metaphyseal chondrodysplasia

A Novel Presentation of Metaphyseal Chondrodysplasia, Schmid Type with Factor VII Deficiency

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