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. 2016 Jun 9:3:16009.
doi: 10.1038/hgv.2016.9. eCollection 2016.

A novel deleterious mutation in the COMP gene that causes pseudoachondroplasia

Huaichao Luo  1 , Sisi Yu  2 , Ying Lin  3 , Qi Guo  4 , Rongchuan Ma  5 , Zimeng Ye  3 , Yanan Di  3 , Ning Li  3 , Yuanying Miao  3 , Yu Zhou  3 , Yuanfeng Li  3 , Jiyun Yang  3 , Zhenglin Yang  6
Affiliations

A novel deleterious mutation in the COMP gene that causes pseudoachondroplasia

Huaichao Luo et al. Hum Genome Var. .

Abstract

Pseudoachondroplasia (PSACH) is a rare and severe genetic disease; therefore, an accurate molecular diagnosis is essential for appropriate disease treatment and family planning. Currently, the diagnosis of PSACH is based mainly on family history, physical examination and radiographic evaluation. Genetic studies of patients with PSACH in Chinese populations have been very limited. With the application of next-generation sequencing (NGS), a comprehensive molecular diagnosis of PSACH is now possible. The purpose of this study was to perform comprehensive NGS-based molecular diagnoses for patients with PSACH in China. We investigated the molecular genetics of one suspected PSACH family in this study. The DNA sample from the proband was sequenced using a custom capture panel that included 249 bone disease genes. Variant calls were filtered and annotated using an in-house automated pipeline. Then, we confirmed the variants by Sanger sequencing in three family members. After co-segregation analysis, the variant, c.1160_1162del of the COMP gene, was identified as a novel mutation responsible for this spontaneous form of PSACH.

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Figures

Figure 1
Figure 1
Pedigree of participating subjects in the study of the suspected PSACH family. Solid symbol indicates affected individuals, open symbols indicate unaffected individuals and the arrow indicates the proband. PSACH, pseudoachondroplasia.
Figure 2
Figure 2
Radiographic findings in the PSACH proband. (a) Radiograph showing anterior beaking of the vertebral bodies. (b) Radiograph of knees. (c) Radiograph showing small femoral heads, flared metaphyseal borders and widened symphysis pubis. (d) Radiograph of ulna and radius. PSACH, pseudoachondroplasia.
Figure 3
Figure 3
Mutation identification of ACAN gene and COMP gene. Electropherogram analysis of ACAN gene and COMP gene in suspected PSACH family showing the co-segregation of the heterozygous mutation c.1160_1162del of the COMP gene with the phenotype. II-1 proband harbored heterozygous alleles, but neither the father I-1 nor the mother I-2 carried this mutation. PSACH, pseudoachondroplasia.
Figure 4
Figure 4
Structural domains of COMP and conservation analysis. (a) Structural domains of COMP and the location of c.1160_1162del are shown by the arrow. (b) Results obtained from HomoloGene showing that residue 387 in the COMP protein is conserved among different species.
See this image and copyright information in PMC

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