Deciphering spinal muscular atrophy through pedigree and molecular genetic analysis

Abstract

Spinal muscular atrophy (SMA) is a severe autosomal recessive neuromuscular disorder characterized by degeneration of anterior horn cells of the spinal cord, leading to progressive muscle weakness and atrophy. It is primarily caused by mutation or deletion in the survival motor neuron-1 gene SMN1 gene on chromosome 5q13.2, resulting in reduced levels of SMN protein, while the SMN2 gene provides only partial compensation. The present study investigated the inheritance pattern and molecular characteristics of SMA in ten clinically diagnosed cases. Clinical histories were collected through patient, family and physician interactions and pedigree charts were constructed to assess inheritance patterns. Molecular diagnosis was performed using genomic DNA analysis, multiplex ligation-dependent probe amplification (MLPA), automated DNA sequencing and multiplex PCR to detect SMN1 gene deletions. The findings revealed that most patients exhibited deletions in exon regions of the SMN1 gene, with six cases showing homozygous deletion of exon 7, two cases showing deletion of both exons 7 and 8 and two cases showing homozygous deletion of exon 7 along with heterozygous deletion of exon 8. Additionally, two patients demonstrated overlapping clinical features of SMA and Duchenne muscular dystrophy (DMD). Pedigree analysis confirmed an autosomal recessive inheritance pattern, with affected individuals born to phenotypically normal carrier parents. The study highlights that homozygous deletion of exon 7 of the SMN1 gene is the most common molecular cause of SMA and emphasizes the importance of molecular genetic testing for accurate diagnosis, carrier detection, prenatal screening and effective genetic counseling.