The phenotypic spectrum in a patient with Glycine to Serine mutation in the <i>COL2A1</i> gene: overview study

Mohammad Shboul; Hela Sassi; Houweyda Jilani; Imen Rejeb; Yasmina Elaribi; Syrine Hizem; Lamia Ben Jemaa; Marwa Hilmi; Susanna Gerit Kircher; Ali Al Kaissi; Mohammad Shboul; Hela Sassi; Houweyda Jilani; Imen Rejeb; Yasmina Elaribi; Syrine Hizem; Lamia Ben Jemaa; Marwa Hilmi; Susanna Gerit Kircher; Ali Al Kaissi

doi:10.3934/molsci.2021006

AIMS Molecular Science

2021, Volume 8, Issue 1: 76-85. doi: 10.3934/molsci.2021006

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Research article

The phenotypic spectrum in a patient with Glycine to Serine mutation in the COL2A1 gene: overview study

1.
Department of Medical Laboratory Sciences, Jordan University of Science and Technology, Irbid, Jordan
2.
Department of Human Genetics, Mongi Slim Hospital Marsa, Tunis, Tunisia
3.
Genetic department, Faculty of Medicine of Tunis, El Manar University, Tunis, Tunisia
4.
Family Medicine Operations, Omar Bin Al Khatab Hospital, Doha, Qatar
5.
Center of Pathobiochemistry and Genetics, Medical University of Vienna, Austria
6.
National Medical Research Center for Traumatology and Ortopedics n.a. G.A. Ilizarov, Kurgan, Russia
7.
Orthopaedic Hospital of Speising, Paediatric Department, Vienna, Austria

Received: 16 December 2020 Accepted: 18 February 2021 Published: 26 February 2021

Objective
Osteochondrodysplasias are a heterogeneous group of genetic skeletal dysplasias. Mutations in the COL2A1 gene cause a spectrum of rare autosomal-dominant type II collagenopathies characterized by skeletal dysplasia, short stature, and with vision and auditory defects. In this study, we have investigated in more detail the phenotypic and genotypic characterization resulting from glycine to serine mutations in the COL2A1 gene in a 2-year-old boy.
Materials and methods
Detailed clinical and radiological phenotypic characterization was the baseline tool to guide the geneticists toward proper genotypic confirmation.
Results
Genetic analysis revealed a de novo mutation, c.1681G>A (p.Gly561Ser), in the collagen type II alpha-1 gene (COL2A1). The identified variant showed impaired protein stability, and lead to dysfunction of type II collagen. In addition to pre and postnatal growth retardation, remarkable retardation of gross motor development and intellectual disability were noted. The latter was connected to cerebral malformations. The overall clinical phenotype of our current patient resembles spondyloepiphyseal dysplasia congenita (SEDC), but with extra phenotypic criteria.
Conclusions
The aim of this paper is twofold; firstly, raising awareness among orthopaedic surgeons when dealing with children manifesting multiple deformities, and secondly to broaden the clinical phenotype in patients with COL2A1 mutations of amino acid substitution (glycine to serine).
- mutation COL2A1,
- spondyloepiphyseal dysplasia congenita,
- extended phenotype
Citation: Mohammad Shboul, Hela Sassi, Houweyda Jilani, Imen Rejeb, Yasmina Elaribi, Syrine Hizem, Lamia Ben Jemaa, Marwa Hilmi, Susanna Gerit Kircher, Ali Al Kaissi. The phenotypic spectrum in a patient with Glycine to Serine mutation in the COL2A1 gene: overview study[J]. AIMS Molecular Science, 2021, 8(1): 76-85. doi: 10.3934/molsci.2021006

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Abstract

Objective

Osteochondrodysplasias are a heterogeneous group of genetic skeletal dysplasias. Mutations in the COL2A1 gene cause a spectrum of rare autosomal-dominant type II collagenopathies characterized by skeletal dysplasia, short stature, and with vision and auditory defects. In this study, we have investigated in more detail the phenotypic and genotypic characterization resulting from glycine to serine mutations in the COL2A1 gene in a 2-year-old boy.

Materials and methods

Detailed clinical and radiological phenotypic characterization was the baseline tool to guide the geneticists toward proper genotypic confirmation.

Results

Genetic analysis revealed a de novo mutation, c.1681G>A (p.Gly561Ser), in the collagen type II alpha-1 gene (COL2A1). The identified variant showed impaired protein stability, and lead to dysfunction of type II collagen. In addition to pre and postnatal growth retardation, remarkable retardation of gross motor development and intellectual disability were noted. The latter was connected to cerebral malformations. The overall clinical phenotype of our current patient resembles spondyloepiphyseal dysplasia congenita (SEDC), but with extra phenotypic criteria.

Conclusions

The aim of this paper is twofold; firstly, raising awareness among orthopaedic surgeons when dealing with children manifesting multiple deformities, and secondly to broaden the clinical phenotype in patients with COL2A1 mutations of amino acid substitution (glycine to serine).

Acknowledgments

We wish to thank Ms. Katharina Sigl, head of the musculo-skeletal group (ordensklinikum) Linz, Austria for her help in facilitating the required investigations.

Author contributions

AAK, LBJ prepare clinical and radiographic documentation, and write the MS. HS, HJ, YE, SH, and MH contributed in patient's and parents investigations. MS and SGK performed screening for lysosomal storage disorders and whole exome sequencing. All authors approved the final version.

Conflict of interest

The authors declare that they have no conflict of interest.

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