Acknowledging the small number of genetic reports used in their study, the researchers attribute the scarce amount of data to a lack of resources and limited access to genetic screening across Africa.
With a gap in knowledge surrounding the genetic landscape of spinal muscular atrophy (SMA) cases in Africa, researchers of a recent study are adding to the limited data on the condition throughout the continent.
Acknowledging the small number of genetic reports used in their study (n = 12), the researchers attribute the scarce amount of data to a lack of resources and limited access to genetic screening across Africa. The group emphasized the importance of detailing the clinical and genetic characteristics of disorders like SMA to help drive expansion of genomic capabilities across the continent.
For example, a high proportion of patients with heterozygous deletion of SMN1 has gained attention, particularly in sub-Saharan Africa.
“There is increasing recognition of SMN1-negative SMA, although this groups accounts for <5% of SMA and is often associated with overlapping central nervous system/brainstem signs, and even cardiomyopathy,” explained the researchers. “However, in reports from Africa there are between 25 and 65% of the clinical cohorts categorised as either congenital hypotonia or SMA phenotypes, which can be categorized as SMN1-negative SMA (absence of homozygous exon 7 deletion).”
The researchers found 5 reports detailing SMA cases in sub-Saharan Africa. Among a cohort of samples from different regions in South Africa, 35%-100% of cases were classical SMA, with homozygous loss of exon 7 (±exons 8).
In another cohort of 300 samples coming from Black patients in sub-Saharan Africa, 2% of patients were heterozygotes. According to the researchers, this finding is similar to that of patients in Kenya and Nigeria but, notably, was half that of patients with European ancestry.
The researchers also found difference in the architecture of SMN2 between African patients and European patients. Among a group of 75 Black South African patients with classical SMA, 11% had more than 2 copies of SMN2, compared with 37% of 30 patients with European ancestry.
“Humans have variable copies of an SMN2 gene, between 0 and 8 copies, and transcripts of this gene can modify the expression of SMN1-SMA. Interestingly, the architecture of the SMN region differs substantially between Europeans and Africans, although African-Americans roughly followed the same trends in terms of SMN2 copy numbers as Europeans and Asians,” wrote the group.
Based on their findings, the researchers suggest a need for further investigation into the differences in genetic architecture and disease pathogenic mechanisms between patients with African ancestry and patients with European ancestry. While variation in SMN2 is not tied to diagnosis of the disease, it can impact the severity of disease and age of onset.
Mahungu A, Monnakgotla N, Nel M, Heckmann J. A review of the genetic spectrum of hereditary spastic paraplegias, inherited neuropathies and spinal muscular atrophies in Africans. Orphanet J Rare Dis. Published online March 24, 2022. doi: 10.1186/s13023-022-02280-2