RESUMEN
Background: GNE myopathy (GM) is a rare autosomal recessive disorder caused by variants in the GNE gene and characterized by progressive distal muscle weakness and atrophy. We report a novel variant in theGNE gene causing GM in a consanguineous Malian family. Case presentation: A 19-year-old male patient from a consanguineous family of Bambara ethnicity was seen for progressive walking difficulty and frequent falls. Neurological examination found distalmuscle weakness and atrophy and reduced tendon reflexes in four limbs. Electroneuromyography (ENMG) showed an axonal neuropathy pattern with reduced distal motor amplitudes. Charcot-Marie-Tooth (CMT) gene panel testing (Medical Neurogenetics LLC, Atlanta, GA) was negative. However, whole exome sequencing (WES) revealed a novel biallelic variant in GNE (c.1838G>A:p.Gly613Glu), segregating with the phenotype in the family. This variant is predicted to be pathogenic by several in silicoprediction tools including CADD= 29. Moreover, protein folding model showed major structural disruptions in the mutant protein. Conclusion: This study reports a novel variant in the GNE gene causing GM, the first molecularly diagnosed in sub-Saharan Africa (SSA). It highlights the diagnosis challenges in this region and broadens the genetic spectrum of this rare disease.
RESUMEN
Key Clinical Message: Cleidocranial dysplasia (CCD) is a rare genetic skeletal disorder with only few cases reported in Africa, mostly based on clinical and radiological findings. We report the first case in Mali, caused by a novel de novo variant in the RUNX2 gene. Abstract: Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal dysplasia characterized by an aplastic/hypoplastic clavicles, patent sutures and fontanels, dental abnormalities and a variety of other skeletal changes. We report a novel de novo variant in the RUNX2 gene causing a severe phenotype of CCD in a Malian girl.