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.

Displasia epifisiaria múltiple: un hallazgo radiológico casual como clave diagnóstica

“…Bajuifer y Letts (2005) describen que entre las alteraciones primarias del crecimiento se encuentra la Displasia Epifisaria Múltiple (DEM), una osteocondrodisplasia caracterizada por anomalías en el desarrollo de las epífisis del hueso, que ocasionan deformidades óseas, afectan a las articulaciones y conducen a la aparición temprana de artrosis. Según Ho et al (2020), es una condición poco común, con incidencia de 1:10.000 NV, aun cuando es una de las osteocondrodisplasias más frecuentes. Stanescu et al (1993) precisan que la DEM se presenta bajo dos fenotipos: una forma severa, tipo Fairbank, caracterizada por epífisis pequeñas, que involucra además en forma considerable la mano y la muñeca del paciente, expresándose como manos cortas y braquidactilia; y una forma moderada o tipo Ribbing, con epífisis aplanadas y mínimo deterioro o sin ninguna afección de mano y muñeca.…”