We undertook in this study the first successful prenatal diagnoses of MDC1A and LGMD2C forms in Africa, with a subsequent postnatal clinical follow-up of the newborns. Genetic and molecular studies were performed on cultured amniotic fluid cells after exclusion of maternal cell contamination. Immunofluorescence on the patients' muscle biopsies was performed so as to study the expression of muscular laminins. Results showed that normal and affected fetuses were diagnosed according to the presence or the absence of the responsible mutation in LAMA2 or SGCG genes. Postnatal molecular and clinical outcome was concordant with all prenatal diagnoses. However, a patient with MDC1A form of congenital muscular dystrophy who was diagnosed as affected was normal at birth, and developed later clinical features different from those observed in his severely affected elder brother. This intrafamilial clinical variability in two siblings occurring with the same mutation in LAMA2 gene emphasizes the importance of the postnatal follow-up in the confirmation of prenatal diagnosis, and suggests that other genetic or epigenetic factors can monitor the course of the MDC1A form.

Metachromatic leukodystrophy (MLD) is a neurodegenerative disorder characterized by progressive demyelination resulting from impaired degradation and thus the accumulation of cerebroside-3-sulfate (sulfatide). It is caused by the deficiency of arylsulfatase A (ARSA) enzyme which is encoded by the ARSA gene. The present study reports the clinical, molecular, and bioinformatic investigation of three patients belonging to a consanguineous family with late-infantile MLD disorder. The results revealed a novel homozygous missense mutation c.699C>A (p.His231Gln) in exon 4 of ARSA gene in the three patients inherited from their heterozygous parents. Interestingly, this novel mutation is the second mutation identified in the substrate-binding site of ARSA protein and it was classified as damaging and deleterious by several bioinformatics tools. The c.699C>A (p.His231Gln) leads to changes in the pre-mRNA secondary structure and in the ARSA protein 3D structure with a significant root mean square deviation value which could probably affect its stability and function.