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

Huang, Xiangjun; Deng, Xiong; Xu, Hongbo; Wu, Song; Yuan, Lamei; Yang, Zhijian; Yang, Yan; Deng, Hao

doi:10.1371/journal.pone.0127529

Cited by 16 publications

(16 citation statements)

References 30 publications

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“…Genomic DNA (gDNA) was extracted from peripheral blood using phenol–chloroform extraction method . Exome sequencing of gDNA from one patient (II:1) was performed by Novogene Bioinformatics Institute, Beijing, China.…”

Section: Methodsmentioning

confidence: 99%

A novel heterozygous COL4A4 missense mutation in a Chinese family with focal segmental glomerulosclerosis

et al. 2016

J Cellular Molecular Medi

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Focal segmental glomerulosclerosis (FSGS) is the most common glomerular histological lesion associated with high‐grade proteinuria and end‐stage renal disease. Histologically, FSGS is characterized by focal segmental sclerosis with foot process effacement. The aim of this study was to identify the disease‐causing mutation in a four‐generation Chinese family with FSGS. A novel missense mutation, c.1856G>A (p.Gly619Asp), in the collagen type IV alpha‐4 gene (COL4A4) was identified in six patients and it co‐segregated with the disease in this family. The variant is predicted to be disease‐causing and results in collagen IV abnormalities. Our finding broadens mutation spectrum of the COL4A4 gene and extends the phenotypic spectrum of collagen IV nephropathies. Our study suggests that exome sequencing is a cost‐effective and efficient approach for identification of disease‐causing mutations in phenotypically complex or equivocal disorders. Timely screening for COL4A3/COL4A4 mutations in patients with familial FSGS may help both accurately diagnose and treat these patients.

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Section: Methodsmentioning

confidence: 99%

A novel heterozygous COL4A4 missense mutation in a Chinese family with focal segmental glomerulosclerosis

et al. 2016

J Cellular Molecular Medi

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“…collagen II is an important component of ECM, and its expression is significantly downregulated during the Idd process (11,12). Mutation of collagen type II alpha 1 chain, the encoding gene of collagen II, is commonly identified in spondyloepiphyseal dysplasia congenita, knee osteoarthritis, kniest dysplasia and type II collagenopathies (13)(14)(15). c-telopeptide of type II collagen (cTX-II) is a degradation product of collagen II, and is usually upregulated in the sera of patients with osteoarthritis (16).…”

Section: Introductionmentioning

confidence: 99%

Bone morphogenetic protein 2 alleviated intervertebral disc degeneration through mediating the degradation of ECM and apoptosis of nucleus pulposus cells via the PI3K/Akt pathway

et al. 2018

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The present study aimed to explore the underlying mechanisms of bone morphogenetic protein 2 (BMP2) in alleviating intervertebral disc degeneration (Idd). A rat puncture Idd model was constructed, and the rats were randomly divided into six groups: control; Idd (model); Idd+PBS [containing 10 10 adeno-associated virus serotype 2 (AAV)]; and Idd + AAV2-BMP2 (10 6 , 10 8 and 10 10 ). IL-1β was used to treat primary nucleus pulposus (NP) cells to mimic Idd in vitro. The effects of BMP2 in Idd were determined by magnetic resonance imaging (MRI), hematoxylin and eosin staining and Alcian Blue staining in vivo. The levels of collagen II, aggrecan, transcription factor SOX9 (SOX9) and matrix metalloproteinase 13 (MMP-13) were examined using western blot analysis and reverse transcription quantitative polymerase chain reaction (RT-qPcR) in NP tissues and cells. The expression of c-telopeptide of type II collagen (cTX-II) in the sera or cell supernatants was determined by ELISA. In addition, the levels of phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt), and the levels of apoptosis-associated proteins and apoptosis ratio of NP cells were also determined by western blot analysis and flow cytometry, respectively. LY29400, an inhibitor of PI3K, was used to additionally confirm the signal pathway mechanism of BMP2 treatment in IDD. BMP2 significantly extended the interval between discs and alleviated the fibrous ring rupture and the decrease in the levels of glycoproteins in Idd rats, as determined by MRI and histological staining. Additionally, BMP2 treatment significantly upregulated the levels of collagen II, aggrecan and SOX9, but downregulated the levels of MMP-13 and cTX-II in Idd rats and NP cells in a dose-dependent manner. concurrently, recombinant human (rh)BMP2 pretreatment also significantly decreased the apoptosis ratio of interleukin (IL)-1β-treated NP cells via downregulating the level of cleaved caspase-3 and upregulating the level of uncleaved poly (adenosine 5'-diphosphate-ribose) polymerase. It was demonstrated that rhBMP2 also significantly decreased the inflammatory response in NP tissues and cells, based on levels of IL-6, TNF-α and IL-10. In addition, rhBMP2 inhibited cell apoptosis via upregulating the phosphorylation levels of the PI3K/Akt signaling pathway, and LY29400 pretreatment inhibited the effects of BMP2 in IL-1β treated NP cells. BMP2 alleviated Idd via the PI3K/Akt signaling pathway by inhibiting NP cell apoptosis and decreasing the levels of matrix proteins.

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“…Exome sequencing was conducted in the proband of this family (VI:2, Fig. A) on the Illumina HiSeq 2000 platform at BGI‐Shenzhen (Shenzhen, China), as previously described . Single nucleotide polymorphisms (SNPs) and small insertions–deletions (indels) in coding sequences or splice sites were identified .…”

Section: Methodsmentioning

confidence: 99%

Compound heterozygous POMT1 mutations in a Chinese family with autosomal recessive muscular dystrophy‐dystroglycanopathy C1

Yuan

et al. 2017

J Cellular Molecular Medi

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Muscular dystrophy‐dystroglycanopathy (MDDG) is a genetically and clinically heterogeneous group of muscular disorders, characterized by congenital muscular dystrophy or later‐onset limb‐girdle muscular dystrophy accompanied by brain and ocular abnormalities, resulting from aberrant alpha‐dystroglycan glycosylation. Exome sequencing and Sanger sequencing were performed on a six‐generation consanguineous Han Chinese family, members of which had autosomal recessive MDDG. Compound heterozygous mutations, c.1338+1G>A (p.H415Kfs*3) and c.1457G>C (p.W486S, rs746849558), in the protein O‐mannosyltransferase 1 gene (POMT1), were identified as the genetic cause. Patients that exhibited milder MDDG manifested as later‐onset progressive proximal pelvic, shoulder girdle and limb muscle weakness, joint contractures, mental retardation and elevated creatine kinase, without structural brain or ocular abnormalities, were further genetically diagnosed as MDDGC1. The POMT1 gene splice‐site mutation (c.1338+1G>A) which leads to exon 13 skipping and results in a truncated protein may contribute to a severe phenotype, while the allelic missense mutation (p.W486S) may reduce MDDG severity. These findings may expand phenotype and mutation spectrum of the POMT1 gene. Clinical diagnosis supplemented with molecular screening may result in more accurate diagnoses of, prognoses for, and improved genetic counselling for this disease.

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

Cited by 16 publications

References 30 publications

A novel heterozygous COL4A4 missense mutation in a Chinese family with focal segmental glomerulosclerosis

A novel heterozygous COL4A4 missense mutation in a Chinese family with focal segmental glomerulosclerosis

Bone morphogenetic protein 2 alleviated intervertebral disc degeneration through mediating the degradation of ECM and apoptosis of nucleus pulposus cells via the PI3K/Akt pathway

Compound heterozygous POMT1 mutations in a Chinese family with autosomal recessive muscular dystrophy‐dystroglycanopathy C1

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