Spondylo-epi-metaphyseal dysplasia due to a homozygous missense mutation in the gene encoding Matrilin-3 (T120M).

Das, Liza; Dhiman, Vandana; Van Hul, Wim; Bhansali, Anil; Gogate, Yashpal; Steenackers, Ellen; Mortier, Geert; Bhadada, Sanjay Kumar · Bone Rep · 2020

case_report · Level V

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Abstract

Spondylo-epi-metaphyseal dysplasia (SEMD) represents a group of osteo-chondrodysplasias characterized by vertebral, epiphyseal as well as metaphyseal abnormalities. Several genes have been identified underlying the different forms. Two relatives (cousins) in a family were found to have disproportionate short stature with clinical and radiological features suggestive of SEMD. Metabolic bone profile was normal including parathyroid hormone and 25(OH)vitamin D3. Exome sequencing revealed a missense mutation (p. T120M) in the von-Willebrand factor A-domain of the Matrilin 3 (<i>MATN3</i>) gene that segregates with the disease in the family. We identified a homozygous missense mutation in <i>MATN3</i>, an important structural component of the extracellular matrix of cartilage, as the genetic cause of SEMD in this pedigree. <i>MATN3</i> mutations have been more commonly associated with multiple epiphyseal dysplasia than SEMD. Recognition of this mutation will aid in enhancing the understanding and expanding the spectrum of this particular skeletal dysplasia.