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Review
. 2017 Aug 26;11(1):237.
doi: 10.1186/s13256-017-1396-y.

A novel mutation in the COL2A1 gene in a patient with Stickler syndrome type 1: a case report and review of the literature

Yousuke Higuchi  1   2 , Kosei Hasegawa  3 , Miho Yamashita  2   4 , Hiroyuki Tanaka  5 , Hirokazu Tsukahara  1
Affiliations
Review

A novel mutation in the COL2A1 gene in a patient with Stickler syndrome type 1: a case report and review of the literature

Yousuke Higuchi et al. J Med Case Rep. .

Abstract

Background: Stickler syndrome is a group of collagenopathies characterized by ophthalmic, skeletal, and orofacial abnormalities, with the degree of symptoms varying among patients. Mutations in the COL2A1, COL11A1, and COL11A2 procollagen genes cause Stickler syndrome. Marshall syndrome, caused by a COL11A1 mutation, has clinical overlap with Stickler syndrome.

Case presentation: A 2-year-old Japanese boy was presented to our hospital with short stature (79.1 cm, -2.52 standard deviation). His past medical history was significant for soft cleft palate and bilateral cataracts. He had a flat midface, micrognathia, and limitations in bilateral elbow flexion. Radiographs showed mild spondyloepiphyseal dysplasia. Initially, we suspected Marshall syndrome, but no mutation was identified in COL11A1. At 8 years old, his height was 116.2 cm (-1.89 standard deviation), and his orofacial characteristics appeared unremarkable. We analyzed the COL2A1 gene and found a novel heterozygous mutation (c.1142 G > A, p.Gly381Asp).

Conclusions: In this case report, we identify a novel missense mutation in the COL2A1 gene in a patient with Stickler syndrome type 1, and we describe age-related changes in the clinical phenotype with regard to orofacial characteristics and height. Genetic analysis is helpful for the diagnosis of this clinically variable and genetically heterogeneous disorder.

Keywords: COL2A1; Marshall syndrome; Stickler syndrome; Type II collagenopathy.

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Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the institutional review board of Okayama University Hospital for clinical research. All procedures performed in studies involving human participants were done in accordance with the 1964 Helsinki declaration and its later amendments.

Consent for publication

Written informed consent was obtained from the patient’s legal guardian(s) for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Radiological images of the patient. Radiographic images show thickening of the calvaria (a); metaphyseal flaring of the distal humerus (b); mild kyphosis (c); and lack of femoral head ossification, deformity of the femoral neck, and distal femoral and proximal tibial epiphyseal ossification centers (d). Reformatted computed tomographic scans of the cervical spine show hypoplasia of dens and separation of the anterior atlas arch (e), as well as abnormal ossification at the spinous process of the axis (f)
Fig. 2
Fig. 2
Growth chart. The patient’s short stature gradually improved over time
Fig. 3
Fig. 3
Mutation analysis of the COL2A1 gene. Heterozygous mutation c.1142G > A (p.Gly381Asp) is denoted by the arrow. The glycine substitution mutation is in the Gly-X-Y triplet repeats region of the type II collagen triple helix (a). The glycine at amino acid 381 is highly conserved throughout species (b)
See this image and copyright information in PMC

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References

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