Molecular study of infantile Spinal Muscular Atrophy

Infantile Spinal Muscular Atrophy (SMA) is a group of autosomal recessive disorders characterized by a degeneration of the motor neurons in the anterior horn of the spinal cord leading to a progressive paralysis of the limbs and trunk with muscle atrophy. 95% of cases are due to exon 7 deletions in the SMN gene. The aim of this work is to determine the frequency of the exon 7 deletion in the SMN1 gene in congenital hypotonia of unknown cause in some Moroccan patients. The exon 7 deletion of the SMN1 gene was investigated in 29 unrelated Moroccan infants. These patients were referred to the genetic consultation for congenital hypotonia during the period from June 2013 to June 2021. The identification of exon 7 deletion was performed using PCR-RFLP. Homozygous deletion was found in 15 infants (52%) while 14 patients had negative results. On the other hand, deletions of NAIP gene and exon 8 of the SMN gene are in progress. The 5q13 region (SMA locus) is composed of two 500 kb elements, duplicated and inverted, each element containing one copy of the SMN gene, one copy of the NAIP gene and one copy of the p44 gene. Deletions of exon 7 of the SMN1 gene cause the accumulation of the abnormal SMN protein and consequently its absence in axonal extensions. Thereby, the identification of this mutation remains important in infants with congenital hypotonia without obvious cause. This easy genetic test should be systematically proposed after a well-established genetic counseling. Keywords: SMN, SMA, Congenital hypotonia, NAIP.