CASE REPORT OF DOUBLE HETEROZYGOUS PATIENTC WITH SPINAL MUSCULAR ATROPHY

  • Danilo Nonkulovski PHI University Clinic for Pediatric Diseases, Faculty of Medicine, Ss.Cyril and Methodius University in Skopje, North Macedonia
  • Filip Duma PHI University Clinic for Pediatric Diseases, Faculty of Medicine, Ss.Cyril and Methodius University in Skopje, North Macedonia
  • Lejla Muaremoska-Kanzoska PHI University Clinic for Pediatric Diseases, Faculty of Medicine, Ss.Cyril and Methodius University in Skopje, North Macedonia
  • Ilija Kirovski PHI University Clinic for Pediatric Diseases, Faculty of Medicine, Ss.Cyril and Methodius University in Skopje, North Macedonia
  • Aspazija Sofijanova PHI University Clinic for Pediatric Diseases, Faculty of Medicine, Ss.Cyril and Methodius University in Skopje, North Macedonia
  • Liljana Zhivkovska PHI University Clinic for Pediatric Diseases, Faculty of Medicine, Ss.Cyril and Methodius University in Skopje, North Macedonia
  • Valentina Dukovska PHI University Clinic for Pediatric Diseases, Faculty of Medicine, Ss.Cyril and Methodius University in Skopje, North Macedonia

Abstract

Spinal muscular atrophy is an autosomal-recessive disorder characterized by degeneration of motor neurons in the spinal cord and caused by mutations in the survival motor neuron 1 gene, SMN1. In most patients with SMA, the disease is caused by a homozygous deletion or mutation. However, approximately 5% of patients present as compound heterozygotes in which they have only one deletion of SMN1 and a subtle mutation of the other chromosome. The phenotype in these rare cases is much milder than the “classic†forms of SMA, which brings bigger challenge regarding the diagnosis. To describe a case of SMA compound heterozygote and discuss the challenges regarding the diagnosis. Patient’s blood was taken for genetic analysis for SMN1 gene. Automatic DNA extraction, using MLPA method. We present a female patient on the age of 15 months, with clinical features and genetically confirmed spinal muscular atrophy type 2. The genetic analysis showed double heterozygosity for deletion of SMN1, inherited from her mother, as well as genetic conversion of the SMN1 to SMN2 pseudo gene, inherited from the father. The analysis also showed absence of the SMN1 gene and presence of 3 copies of the SMN2 pseudo gene. Fortunately, at our department we are able to treat SMA patients with oral  (Risdiplam) and intrathecal therapy (Nusinersen), which both have shown particular improvement in these patients. Accurate diagnosis of SMA is challenging for compound heterozygotes, but is crucial now, as treatments and gene therapy have become available.


Keywords: SMN1 gene, heterozygous, mutation, deletion.


https://doi.org/10.55302/JMS2361062n

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Published
2023-05-10
How to Cite
NONKULOVSKI, Danilo et al. CASE REPORT OF DOUBLE HETEROZYGOUS PATIENTC WITH SPINAL MUSCULAR ATROPHY. Journal of Morphological Sciences, [S.l.], v. 6, n. 1, p. 62-67, may 2023. ISSN 2545-4706. Available at: <https://jms.mk/jms/article/view/vol6no1-8>. Date accessed: 19 june 2024.
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Articles