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

• Published in: BMC musculoskeletal disorders Vol. 21; no. 1; p. 216
• Main Authors: Ho, Thuong Thi, Tran, Linh Huyen, Hoang, Lan Thu, Doan, Phuong Kim Thi, Nguyen, Trang Thi, Nguyen, Trang Hong, Tran, Hoai Thu, Hoang, Ha, Chu, Ha Hoang, Luong, Anh Lan Thi
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 07-04-2020; BioMed Central; BMC
• Subjects: Asian Continental Ancestry Group - genetics; Bone dysplasia; Cartilage; Case Report; Case reports; Child; Collagen (type IX); de novo missense variant; Deoxyribonucleic acid; DNA; DNA sequencing; Dysplasia; Epiphysis; Exons; Exons - genetics; Families & family life; Family; Female; Femur; Genes; Genetic aspects; Genetic testing; Genomes; Genomics; Heterozygous; Hip; Humans; Knee; Limbs; MATN3; Matrilin Proteins - genetics; Multiple epiphyseal dysplasia; Mutation; Mutation, Missense; Osteochondrodysplasias - diagnostic imaging; Osteochondrodysplasias - genetics; P.A191D matrilin-3; Pedigree; Proteins; Radiography; Scientific equipment industry; Skeleton; Vietnamese case; United States; Vietnam; United States > US; Multiple epiphyseal dysplasia; P.A191D matrilin-3; de novo missense variant; Vietnamese case; Heterozygous; MATN3
• ISSN: 1471-2474; 1471-2474
• DOI: 10.1186/s12891-020-03222-4

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.
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.
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.