SERF1A – Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a well‐characterized autosomal recessive neuromuscular disorder most commonly caused by homozygous deletions or mutations in SMN1. In recent multi‑patient studies, SERF1A (HGNC:10755) has been included among a panel of candidate modifying genes assessed for potential contributions to the variable SMA phenotype (PMID:21821450) (PMID:23352792).

Current evidence supporting a direct gene‑disease association for SERF1A with SMA remains limited. Although these studies examined several genes within the SMN1 region, no pathogenic variants or clear segregation data have been reported for SERF1A. The overall evaluation based on available data is therefore categorized as Limited, despite a reasonable sample size that was analyzed in the context of candidate modifying effects (PMID:21821450).

Genetic evidence for SERF1A is primarily derived from its inclusion in multi‑patient cohort analyses, where its copy number or expression was concurrently measured alongside other established SMA‑related genes. No specific SERF1A variants meeting the rigorous HGVS criteria (e.g., a coding change starting with ‘c.’ and including an amino‑acid consequence such as p.SerXYZ) were reported; hence, the variant evidence field remains unpopulated. Furthermore, there were no reported affected relatives showing segregation for SERF1A‐specific changes.

There is also a notable absence of experimental studies specifically addressing the role of SERF1A in SMA pathogenesis. No functional assays, animal models, or cell‑based studies have been published that directly support a mechanism of pathogenicity for SERF1A in the context of SMA, such as haploinsufficiency or dominant‑negative effects. Consequently, the available functional evidence for SERF1A in SMA is likewise classified as Limited.

Integrating the genetic and experimental data, the current evidence does not definitively support a causative role for SERF1A in SMA. Its inclusion in candidate gene panels reflects an interest in potential modifier effects; however, the lack of reported pathogenic variants, robust segregation data, or functional validation precludes a stronger association at this time.

Key take‑home sentence: While SERF1A is a candidate gene within the SMA genomic region, its current limited genetic and functional evidence restricts its clinical utility in SMA diagnostic decision‑making, underscoring the need for further targeted studies.

References

• European journal of paediatric neurology : EJPN • 2012 • Correlation of SMN2, NAIP, p44, H4F5 and Occludin genes copy number with spinal muscular atrophy phenotype in Tunisian patients PMID:21821450
• Journal not provided • Year not provided • Study on SMA modifying genes PMID:23352792

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