Novel mutations in the COL2A1 gene in Japanese patients with Stickler syndrome

Kondo, Hiroyuki; Matsushita, Itsuka; Nagata, Tatsuo; Hayashi, Takaaki; Kakinoki, Masashi; Uchio, Eiichi; Kondo, Mineo; Ohji, Masahito

doi:10.1038/hgv.2016.18

Cited by 18 publications

(9 citation statements)

References 11 publications

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“…Richards et al focused on the exon 2 and found that the phenotypes, which resulted from COL2A1 variants in exon 2, are characterized by predominantly ocular disorders (eg, retinal detachment) . STL 1 has a higher incidence than other type II collagenopathies, and large cohorts of patients have been previously examined by researchers in numerous countries . Wagner disease (MIM #143200) is a rare vitreoretinal degeneration, which is usually caused by mutation of VCAN .…”

Section: Resultsmentioning

confidence: 94%

Integrated analysis of COL2A1 variant data and classification of type II collagenopathies

Zhang

et al. 2019

Clinical Genetics

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The COL2A1 gene encodes the alpha‐1 chain of type II procollagen. Type II collagen, comprised of three identical alpha‐1 chains, is the major component of cartilage. COL2A1 gene variants are the etiologies of genetic diseases, termed type II collagenopathies, with a wide spectrum of clinical presentations. To date, at least 460 distinct COL2A1 mutations, identified in 663 independent probands, and 21 definite disorders have been reported. Nevertheless, a well‐defined genotype‐phenotype correlation has not been established, and few hot spots of mutation have been reported. In this study, we analyzed data of COL2A1 variants and clinical information of patients obtained from the Leiden Open Variation Database 3.0, as well as the currently available relevant literature. We determined the characteristics of the COL2A1 variants and distributions of the clinical manifestations in patients, and identified four likely genotype‐phenotype correlations. Moreover, we classified 21 COL2A1‐related disorders into five categories, which may assist clinicians in understanding the essence of these complex phenotypes and prompt genetic screening in clinical practice.

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Section: Resultsmentioning

confidence: 94%

Integrated analysis of COL2A1 variant data and classification of type II collagenopathies

Zhang

et al. 2019

Clinical Genetics

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“…The clinical findings and mutations in the COL2A1 gene of 21 of the patients have been reported in detail. 2 , 15 – 17 The remaining five patients were newly studied, and the associated mutations in the COL2A1 gene were c.3624del (predicted to p.Gly1209Valfs*18, NM_001844.4) for Patient 1, c.3188_3211delinsGT (p.Ala1063Glyfs*60) for Patient 6, c.2353C>T (p.Arg785*) for Patient 7, and c.1957C>T (p.Arg653*) for Patient 2. Patient 25 was a family member of Patient 24.…”

Section: Methodsmentioning

confidence: 99%

“…About 80% to 90% of the cases are caused by mutations in the COL2A1 gene. 2 – 4 The ocular features of Stickler syndrome are characterized by high myopia, retinal detachments, vitreous degeneration, and presenile cataracts. 1 – 4 …”

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confidence: 99%

Ultra-Wide Field Fundus Autofluorescence Imaging of Eyes With Stickler Syndrome

Fujimoto

Nagata

Matsushita

et al. 2020

Retina

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“…Although the affected patients in the present study had different genetic mutations, they exhibited similar clinical presentations of retinal detachment and degeneration. Previous studies have also reported that different mutations in COL2A1 can lead to similar phenotypes, with various degrees of expressivity ( 42 , 49 ). The majority of COL2A1 mutations identified in Stickler syndrome are loss-of-function mutations, as they are predicted to result in nonsense-mediated decay of transcripts ( 42 ).…”

Section: Discussionmentioning

confidence: 86%

Targeted next‑generation sequencing identifies two novel COL2A1 gene mutations in Stickler syndrome with bilateral retinal detachment

et al. 2018

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Stickler syndrome is a group of inherited connective tissue disorders characterized by distinctive facial and ocular abnormalities, hearing loss and early-onset arthritis. The aim of the present study was to investigate the genetic changes in two Chinese patients with Stickler syndrome, manifested as bilateral retinal detachment and peripheral retinal degeneration. Complete ophthalmic examinations, including best-corrected visual acuity, slit-lamp examination and fundus examination, were performed. Genomic DNA was extracted from leukocytes of the peripheral blood collected from the patients, their unaffected family members and 200 unrelated control subjects from the same population. Next-generation sequencing of established genes associated with ocular disease was performed. A heterozygous collagen type II α1 chain (COL2A1) mutation c.1310G>C (p.R437P) in exon 21 was identified in Family 1 and a heterozygous COL2A1 mutation c.2302-1G>A in intron 34 was identified in Family 2. The functional effects of the mutations were assessed by polymorphism phenotyping (PolyPhen) and sorting intolerant from tolerant (SIFT) analysis. The c.1310G>C mutation was predicted to damage protein structure and function, and the c.2302-1G>A mutation was predicted to result in a splicing defect. The findings of the current study expand the established mutation spectrum of COL2A1, and may facilitate genetic counseling and development of therapeutic strategies for patients with Stickler syndrome.

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Novel mutations in the COL2A1 gene in Japanese patients with Stickler syndrome

Cited by 18 publications

References 11 publications

Integrated analysis of COL2A1 variant data and classification of type II collagenopathies

Integrated analysis of COL2A1 variant data and classification of type II collagenopathies

Ultra-Wide Field Fundus Autofluorescence Imaging of Eyes With Stickler Syndrome

Targeted next‑generation sequencing identifies two novel COL2A1 gene mutations in Stickler syndrome with bilateral retinal detachment

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