A novel homozygous missense variant in MATN3 causes spondylo-epimetaphyseal dysplasia Matrilin 3 type in a consanguineous family |
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| Affiliation: | 1. Laboratory of Analytical Chemistry and Bromatology, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Morocco;2. Cátedra de Química General, Instituto de Química Inorgánica, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Ayacucho 471, 4000, Tucumán, Argentina;3. Institute of Molecular Biology and Biotechnology/(IMBB), The University of Lahore, Lahore, 54000, Pakistan;4. Equipe de Chimie des Plantes et de Synthèse Organique et Bioorganique, URAC23, Faculty of Science, B.P. 1014, Geophysics, Natural Patrimony and Green Chemistry (GEOPAC) Research Center, Mohammed V University in Rabat, Morocco;5. Mohammed VI Polytechnic University, Lot 660, Hay Moulay Rachid, Benguerir, Morocco;6. Laboratory of Applied Chemistry and Environment (LCAE), Department of Chemistry, Faculty of Sciences, University Mohamed Premier, Oujda 60000, Morocco;7. Inorganic Chemistry Department, Faculty of Chemistry, University of Bucharest, Dumbrava Rosie 23, Bucharest 020462, Romania;8. Institute of Condensed Matter and Nanosciences, Molecular Chemistry, Materials and Catalysis (IMCN/MOST), Université catholique de Louvain, Place L. Pasteur 1, 1348 Louvain-la-Neuve, Belgium;9. Laboratory of Medicinal Chemistry, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco;1. Department of Chemistry, Kongju National University, Gongju, Chungnam 32588, Republic of Korea;2. Department of Biological Sciences, Kongju National University, Gongju, Chungnam 32588, Republic of Korea;3. Institute of Molecular Biology and Biotechnology, The University of Lahore, 54590, Pakistan |
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| Abstract: | Spondylo-epimetaphyseal dysplasia Matrilin 3 type (SEMD) is a rare autosomal recessive skeletal dysplasia characterized by short stature, abnormalities in the vertebral bodies and long bones, especially the lower limbs. We enrolled a consanguineous family from Pakistan in which multiple siblings suffered from severe skeletal dysplasia. The six affected subjects ranged in heights from 100 to 136 cm (~-6 standard deviation). Lower limb abnormalities with variable varus and valgus deformities and joint dysplasia were predominant features of the clinical presentation. Whole exome sequencing (WES) followed by Sanger sequencing identified a missense variant, c.542G > A, p.(Arg181Gln) in MATN3 as the genetic cause of the disorder. The variant was homozygous in all affected individuals while the obligate carriers had normal heights with no skeletal symptoms, consistent with a recessive pattern of inheritance. Multiple sequence alignment revealed that MATN3 domain affected by the variant is highly conserved in orthologous proteins. The c.542G > A, p.(Arg181Gln) variant is only the fourth variant in MATN3 causing an autosomal recessive disorder and thus expands the genotypic spectrum. |
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| Keywords: | Exome sequencing Pakistan SEMD Short stature Skeletal dysplasia |
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