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A novel de novo mutation in COL2A1 leading to spondyloepiphyseal dysplasia congenita in a Chinese family.

ABSTRACT: Spondyloepiphyseal dysplasia congenita (SEDC) is an extremely rare autosomal dominant chondrodysplasia that is usually caused by substitution of glycine with another amino acid in the triple helical region of COL2A1. Herein, we describe a case of SEDC in a Chinese family with a novel de novo mutation in the COL2A1 gene, c.1150G>A (p.Gly384Ser), which may impair protein stability and lead to dysfunction of type II collagen.

SUBMITTER: Xiong Q

PROVIDER: S-EPMC5763142 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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A novel de novo mutation in COL2A1 leading to spondyloepiphyseal dysplasia congenita in a Chinese family.

Xiong Qiuhong Q Liu Yi Y Xue Yu Y Liu Shichao S Wang Jing J Li Ping P Wu Changxin C Yang Yanling Y Xiao Han H

Human genome variation 20180111

Spondyloepiphyseal dysplasia congenita (SEDC) is an extremely rare autosomal dominant chondrodysplasia that is usually caused by substitution of glycine with another amino acid in the triple helical region of COL2A1. Herein, we describe a case of SEDC in a Chinese family with a novel de novo mutation in the COL2A1 gene, c.1150G>A (p.Gly384Ser), which may impair protein stability and lead to dysfunction of type II collagen. ...[more]

PMID: 29354277

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A novel COL2A1 mutation causing spondyloepiphyseal dysplasia congenita in a Chinese family.

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Identification of a Novel Mutation in the COL2A1 Gene in a Chinese Family with Spondyloepiphyseal Dysplasia Congenita.

Project description:Spondyloepiphyseal dysplasia congenita (SEDC) is an autosomal dominant chondrodysplasia characterized by disproportionate short-trunk dwarfism, skeletal and vertebral deformities. Exome sequencing and Sanger sequencing were performed in a Chinese Han family with typical SEDC, and a novel mutation, c.620G>A (p.Gly207Glu), in the collagen type II alpha-1 gene (COL2A1) was identified. The mutation may impair protein stability, and lead to dysfunction of type II collagen. Family-based study suggested that the mutation is a de novo mutation. Our study extends the mutation spectrum of SEDC and confirms genotype-phenotype relationship between mutations at glycine in the triple helix of the alpha-1(II) chains of the COL2A1 and clinical findings of SEDC, which may be helpful in the genetic counseling of patients with SEDC.

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Identification of an Autosomal Dominant Mutation in the COL2A1 Gene Leading to Spondyloepiphyseal Dysplasia Congenita in a Greek Family.

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Novel COL2A1 variants in Japanese patients with spondyloepiphyseal dysplasia congenita.

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Discovery of sensorineural hearing loss and ossicle deformity in a Chinese Li nationality family with spondyloepiphyseal dysplasia congenita caused by p.G504S mutation of COL2A1.

Project description:BackgroundSpondyloepiphyseal dysplasia congenita (SEDC) is an autosomal dominant chondrodysplasia characterized by disproportionate short stature, abnormal epiphyses, and flattened vertebral bodies. COL2A1 has been confirmed as the pathogenic gene. Hearing loss represents an infrequent manifestation for 25-30% of patients with SEDC. The characteristics of the hearing impairment were rarely documented.MethodsAudiological, ophthalmic, imaging examinations were conducted on the family members. The whole exome sequencing (WES) was performed to detect the candidate gene, and the Sanger sequencing was used to confirm the causative variation.ResultsCOL2A1 c.1510G>A (p.G504S), a hot spot variation, was identified as the disease-causing mutation of the Chinese Li nationality family with SEDC. This variation was co-segregated with the SEDC phenotype in the family and was absent in the 1000 Genomes Project, ESP and ExAC. Clinically, several manifestations were first demonstrated in SEDC patients caused by p.G504S, including sensorineural hearing loss, auditory ossicles deformity, retinal detachment, sacrum cracked and elbow and wrist joints deformity. Other classical SEDC manifestations such as bones and joints pain, midfacial dysplasia, disproportionate short stature, spinal deformity, thoracocyllosis, coxa arthropathy, myopia and waddling gait were also showed in the family patients.ConclusionWe first identified the mutation p.G504S in COL2A1 gene as the pathogenesis in a Chinese Li nationality family and reported the correlation between p.G504S and atypical clinical phenotypes including sensorineural hearing loss, auditory ossicles deformity, retinal detachment, sacrum cracked and elbow and wrist joints deformity. Our findings would extend the phenotypic spectrum of SEDC and deepen clinicians' understanding of genotype-phenotype correlation of the disease.

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A missense mutation in the mouse Col2a1 gene causes spondyloepiphyseal dysplasia congenita, hearing loss, and retinoschisis.

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IPSC reprogramming of two patients with spondyloepiphyseal dysplasia congenita (SEDC).

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