A pilot study of spinal muscular atrophy carrier screening in Saudi Arabia

Abstract

Spinal muscular atrophy (SMA), an autosomal recessive inherited disease, is a leading genetic killer under the age of two years. This disease is caused by mutation in the telomeric copy of the survival motor neuron gene (SMN1). Most carriers of SMA have one chromosome 5 with a normal SMN1 gene and one with a deleted SMN1 gene. Although no large-scale population-based studies has been done in Saudi Arabia, previous estimations have indicated that incidence of SMA is much higher in Saudi population compared with other ethnic groups, partly because of high prevalence of consanguineous marriages. In this pilot study, we used a highly sensitive quantitative-polymerase chain reaction method to detect SMA carriers. Among 187 normal individuals not related to an SMA patient the carrier frequency was 5%, i.e. one carrier in each 20 persons compared to one in 50?80 in other parts of the world. Based on the results of this pilot study a new project is designed to further analyze the carrier status of SMA in Saudi population. This will shed more light on the magnitude of the problem of SMA in the countries with high rate of consanguinity.

Genetics of low spinal muscular atrophy carrier frequency in sub‐Saharan Africa

“…For example, studies in Saudi Arabia and Egypt found an SMA carrier frequency of 1 in 20. [36][37][38] Finally, high SMN1 copy numbers in sub-Saharan Africans may be due to the bottleneck phenomenon, meaning that by chance the population that migrated out of Africa to Asia and Europe had lower SMN1 copy number or randomly drifted in this direction after the outmigration. 39 This may be the most likely explanation for the different SMN1 distributions in these areas.…”

A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort

“…While the reported carrier frequency of SMA in the US, Australia, Europe, and the UK is 1:40-80, it has been reported to be much higher (∼1:20) in many parts of the Middle East and North Africa regions [16][17][18][19][20][21]. Based on a calculated average number of births per year for the 20-year period covered by this study using population (World Bank) and birth rate (UNICEF) data, we estimate a high annual incidence of ∼1 in 7,500 individuals with SMA in Lebanon.…”

Unveiling the Genetic Tapestry: Rare Disease Genomics of Spinal Muscular Atrophy and Phenylketonuria Proteins

“…PAH_3 and PAH_6 were outliers while SMN_43 were away from the rest of SMN1 sequences. Clusters Sequences (PAH) Cluster-1 {17, 19,16,32,22,23,24,25,26,29,28,20,21,1,2,49,37,39,38,45,40,41,42,43,10,11,12 In summary, structural and physicochemical analyses provide valuable insights into the structural relationships and disparities among the examined PAH and SMN1 sequences. Clustering analyses reveal evolutionary relationships and potential functional similarities, while the identification of structural features informs their roles in biochemical pathways.…”

“…The PAH gene comprises three distinct domains [24]: The Regulatory N-terminal domain (amino acids 1-142) The Catalytic central domain (amino acids 143-410) The Oligomerization domain, C-terminal, which includes dimerization and tetramerization motifs (amino acids 411-452). Spinal Muscular Atrophy (SMA) is also an autosomal recessive disorder characterized by the loss of motor neurons in the spinal cord and lower brainstem, leading to muscle weakening and atrophy [25, 26, 27]. Recent research has indicated a significant prevalence of SMA in Saudi Arabia, where the numbers hover around 32 in 100,000 births, exceeding global rates [28, 29]. SMA, like many rare diseases, has a genetic basis [30].…”

“…Spinal Muscular Atrophy (SMA) is also an autosomal recessive disorder characterized by the loss of motor neurons in the spinal cord and lower brainstem, leading to muscle weakening and atrophy [25,26,27]. Recent research has indicated a significant prevalence of SMA in Saudi Arabia, where the numbers hover around 32 in 100,000 births, exceeding global rates [28,29]. SMA, like many rare diseases, has a genetic basis [30].…”