Detection, confirmation and gene expression studies of disease causing variants from the whole exome sequencing data of twins with multiminicore disease.

Multiminicore Disase (MmD) is a rare genetic disease which is one of the structural congenital myopathies. The incidence of MmD is not known. There are publications showing the existence of different hereditary forms in different genes related to MmD. Generally, the disease is diagnosed by histopathological and clinical findings. Histopathological examinations with oxidative stainings, show multiple non-staining cores in the muscle tissue. Although different clinical findings may be observed; respiratory failure, motor developmental retardation, muscle weakness are shared clinical findings. The molecular basis of MmD disease and its mechanisms have not been fully elucidated. To date, variants in RYR1, SEPN1, MYH7, TTN, MEGF10 and ACADS genes were associated with the disease. In this study, whole exome sequencing data were analysed for twins with MmD disease and their parents who were first degree consanguineous. Thereby, it was intended to identify, disease causing variant(s). A disease causing variant (c.817G>A/p.G273R) which was not previously associated with MmD in the SEPN1 gene was determined. According to the evaluations, this variant was considered to be likely pathogenic. The identified variant was confirmed by Sanger sequencing in all individuals. SEPN1 gene expression levels were studied. It was not statistically significant. As a result the defined variant in SEPN1 gene in these twins with MmD disease made it possible to give genetic counseling to the family for the future. In addition, our study contributes to the molecular pathogenesis of MmD disease.