Whole exome sequencing identified a pathogenic mutation of COL2A1 causing Stickler syndrome in a Vietnamese family

Authors

  • Nguyen Dang Ton Institute of genome research, Vietnam Academy of Science and Technology
  • Pham Minh Chau
  • Duong Thu Trang
  • Nguyen Thi Xuan
  • Nguyen Xuan Hiep
  • Nguyen Hai Ha

DOI:

https://doi.org/10.15625/1811-4989/18/4/15728

Keywords:

Whole Exome Sequencing (WES), Stickler syndrome, COL2A1 gene, congenital high myopia, retinal detachment

Abstract

Stickler syndrome is a group of rare inherited diseases associated with abnormalities in connective tissues, specifically collagen of the eyes, ears, craniofacies, skeleton and joints. The inheritance pattern of this disease is either an autosomal dominant or an autosomal recessive based on the causative gene. Stickler syndrome is characterized by severe nearsightedness, vitreous abnormalities, distinctive facial features, hearing problems and joint anomalies. Herein, we report a case of a 37-year-old man from Vietnam suspected of Stickler syndrome, presenting a phenotype of retinal detachment and complete loss of vision, and his 3-year-old son with congenital high myopia and vitreous abnormalities. Genetic analysis using whole exome sequencing (WES) revealed a nucleotide substitution (c.C2818T/p.R940X) in exon 42 of the COL2A1 gene that was previously reported as a pathogenic variant causing Stickler syndrome. Validation of COL2A1 c.C2818T in all members of this family by using Sanger sequencing detected the presence of this pathogenic variant in the heterozygous form in the affected father and son but not in the mother and another son without any signs of a vision problem. Thus, our study contributes to not only the knowledge base of clinical and genetic aspects of Stickler syndrome in Vietnam but also the awareness of the importance of genetic counseling in patients with COL2A1 c.C2818T mutation, as well as early diagnosis and appropriate treatment to prevent serious complications, especially blindness.

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Author Biography

Nguyen Dang Ton, Institute of genome research, Vietnam Academy of Science and Technology

The authors have no conflicts of interest 

References

Ahmad, Nilofer Nina et al. 1991. “Stop Codon in the Procollagen II Gene (COL2A1) in a Family with the Stickler Syndrome (Arthro-Ophthalmopathy).” Proceedings of the National Academy of Sciences of the United States of America 88(15): 6624–27. http://www.pnas.org/cgi/doi/10.1073/pnas.88.15.6624 (November 27, 2020).

“All Variants in the COL2A1 Gene - Global Variome Shared LOVD.” https://databases.lovd.nl/shared/variants/COL2A1 (November 27, 2020).

“COL2A1 Collagen Type II Alpha 1 Chain [Homo Sapiens (Human)] - Gene - NCBI.” https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=1280 (November 16, 2020).

“COL2A1 Gene: MedlinePlus Genetics.” https://medlineplus.gov/genetics/gene/col2a1/ (November 27, 2020).

Gelse, K., E. Pöschl, and T. Aigner. 2003. “Collagens - Structure, Function, and Biosynthesis.” Advanced Drug Delivery Reviews 55(12): 1531–46. https://linkinghub.elsevier.com/retrieve/pii/S0169409X03001820 (November 27, 2020).

Kondo, Hiroyuki et al. 2016. “Novel Mutations in the COL2A1 Gene in Japanese Patients with Stickler Syndrome.” Human Genome Variation 3(1): 16018. http://www.nature.com/articles/hgv201618 (November 9, 2020).

Shapiro, MichaelJ et al. 2018. “The Importance of Early Diagnosis of Stickler Syndrome: Finding Opportunities for Preventing Blindness.” Taiwan Journal of Ophthalmology 8(4): 189. /pmc/articles/PMC6302565/?report=abstract (November 23, 2020).

Snead, Martin P., and John R.W. Yates. 1999. “Clinical and Molecular Genetics of Stickler Syndrome.” Journal of Medical Genetics 36(5): 353–59. http://jmg.bmj.com/ (November 19, 2020).

Spranger, J., A. Winterpacht, and B. Zabel. 1994. “The Type II Collagenopathies: A Spectrum of Chondrodysplasias.” European Journal of Pediatrics 153(2): 56–65. https://pubmed.ncbi.nlm.nih.gov/8157027/ (November 17, 2020).

STICKLER, G. B. et al. 1965. “HEREDITARY PROGRESSIVE ARTHRO-OPHTHALMOPATHY.” Mayo Clinic proceedings. Mayo Clinic 40: 433–55. https://pubmed.ncbi.nlm.nih.gov/14299791/ (November 11, 2020).

Stickler, Gunnar B., Wendy Hughes, and Pat Houchin. 2001. “Clinical Features of Hereditary Progressive Arthroophthalmopathy (Stickler Syndrome): A Survey.” Genetics in Medicine 3(3): 192–96. https://www.nature.com/articles/gim200141 (November 25, 2020).

“Stickler Syndrome - GeneReviews® - NCBI Bookshelf.” https://www.ncbi.nlm.nih.gov/books/NBK1302/ (November 24, 2020).

“Stickler Syndrome - NORD (National Organization for Rare Disorders).” https://rarediseases.org/rare-diseases/stickler-syndrome/ (November 27, 2020).

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Published

2021-05-24

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