A novel p.A191D matrilin-3 variant in a Vietnamese family with multiple epiphyseal dysplasia: a case report.

Abstract

BACKGROUND:

Multiple epiphyseal dysplasia (MED) is a common skeletal dysplasia that is characterized by variable degrees of epiphyseal abnormality primarily involving the hip and knee joints. Mutations in a gene encoding matrilin-3 (MATN3) have been reported as disease causing of autosomal dominant MED. The current study identified a novel c.572 C > A variant (p.A191D) in exon 2 of MATN3 in a Vietnamese family with MED.

CASE PRESENTATION:

A standard clinical tests and radiological examination were performed in an 8-year-old Vietnamese girl patient. The clinical examination showed that patient height was under average, with bent lower limbs, limited mobility and dislocation of the joints at both knees. Radiological documentation revealed abnormal cartilage development at the epiphysis of the femur and patella. The patient has a varus deformity of the lower limbs. The patient was diagnosed with autosomal dominant MED using molecular testing in the order of the coding sequences and flanking sequences of five genes: COMP (exons 8-19), MATN3 (exon 2), COL9A2 (exon 3), COL9A3 (exon 3), COL9A1 (exon 8) by Sanger sequencing. A novel heterozygous missense variant (c.572 C > A, p.A191D) in MATN3 was identified in this family, which were not inherited from parents. The p.A191D was predicted and classified as a pathogenic variant. When the two predicted structures of the wild type and mutant matrilin-3 were compared, the p.A191D substitution caused conformational changes near the substitution site, resulting in deformity of the β-sheet of the single A domain of matrilin- 3.

CONCLUSIONS:

This is the first Vietnamese MED family attributed to p.A191D matrilin-3 variant, and our clinical, radiological and molecular data suggest that the novel de novo missense variant in MATN3 contributed to MED.

• Authors: Thuong Thi Ho, Linh Huyen Tran, Lan Thu Hoang, Phuong Kim Thi Doan, Trang Thi Nguyen, Trang Hong Nguyen, Hoai Thu Tran, Ha Hoang, Ha Hoang Chu, Anh Lan Thi Luong
• Journal: BMC musculoskeletal disorders (BMC Musculoskelet Disord) Vol. 21 Issue 1 Pg. 216 (Apr 07 2020) ISSN: 1471-2474 [Electronic] England
• PMID: 32264862 (Publication Type: Case Reports, Journal Article)

Chemical References

• MATN3 protein, human
• Matrilin Proteins

Topics

• Asian People (genetics)
• Child
• Exons (genetics)
• Family
• Female
• Humans
• Matrilin Proteins (genetics)
• Mutation, Missense
• Osteochondrodysplasias (diagnostic imaging, genetics)
• Pedigree
• Radiography