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Case Reports
. 2016 Dec 12;17(1):96.
doi: 10.1186/s12881-016-0357-4.

Short stature, platyspondyly, hip dysplasia, and retinal detachment: an atypical type II collagenopathy caused by a novel mutation in the C-propeptide region of COL2A1: a case report

Apiruk Sangsin  1   2   3   4 , Chalurmpon Srichomthong  1   2 , Monnat Pongpanich  5   6 , Kanya Suphapeetiporn  7   8   9 , Vorasuk Shotelersuk  1   2
Affiliations
Case Reports

Short stature, platyspondyly, hip dysplasia, and retinal detachment: an atypical type II collagenopathy caused by a novel mutation in the C-propeptide region of COL2A1: a case report

Apiruk Sangsin et al. BMC Med Genet. .

Abstract

Background: Heterozygous mutations in COL2A1 create a spectrum of clinical entities called type II collagenopathies that range from in utero lethal to relatively mild conditions which become apparent only during adulthood. We aimed to characterize the clinical, radiological, and molecular features of a family with an atypical type II collagenopathy.

Case presentation: A family with three affected males in three generations was described. Prominent clinical findings included short stature with platyspondyly, flat midface and Pierre Robin sequence, severe dysplasia of the proximal femora, and severe retinopathy that could lead to blindness. By whole exome sequencing, a novel heterozygous deletion, c.4161_4165del, in COL2A1 was identified. The phenotype is atypical for those described for mutations in the C-propeptide region of COL2A1.

Conclusions: We have described an atypical type II collagenopathy caused by a novel out-of-frame deletion in the C-propeptide region of COL2A1. Of all the reported truncating mutations in the C-propeptide region that result in short-stature type II collagenopathies, this mutation is the farthest from the C-terminal of COL2A1.

Keywords: C-propeptide region; COL2A1; Exome sequencing; Type II collagenopathies.

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Figures

Fig. 1
Fig. 1
Pedigree of the index family. The arrow indicates the proband
Fig. 2
Fig. 2
a Photograph of the proband (IV: 3) showing flattened facial profile, micrognathia, short neck, and short trunk. b Whole spine lateral radiograph showing oval-shaped vertebral bodies. c Pelvis, femur, and tibial AP radiograph showing retarded ossification of the femoral heads while other ossification centers are age-appropriate. d Chest radiograph showing age-appropriate ossification centers at humeral heads and greater tuberosities of humeri. e, f Hand and foot AP radiographs are normal
Fig. 3
Fig. 3
a Photograph of proband’s father (III: 1) showing disproportionate short stature and barrel-shaped chest. b, c Hand and feet radiographs are normal without brachydactyly. d Lateral radiograph of the thoracolumbar spine shows platyspondyly with kyphotic deformity. e Pelvis AP radiograph showing severe hip dysplasia and dislocation. f Thoracolumbar spine and pelvis AP radiographs of the proband’s grandfather also show platyspondyly and severe hip dysplasia and dislocation
Fig. 4
Fig. 4
Mutation analysis. a Direct sequencing shows that the proband is heterozygous for a five nucleotide out-of-frame deletion (NM_001844.4: c.4161_4165del:p.Gln1387His*fs30). b Map of the mutations in the C-propeptide region of COL2A1. Truncating mutations shown above the gene lead to collagenopathies with short stature, while those shown below the gene lead to disorders with normal stature. The arrowheads points to the last amino acid residue of the predicted truncated COL2A1. Green: STLI; purple: early-onset OA; red: our mutation; yellow: SPPD; blue: PLSDT. Numbers correspond to Table 2
See this image and copyright information in PMC

References

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