SNRPB – Neurodevelopmental Disorder

Evidence linking SNRPB (HGNC:11153) to neurodevelopmental disorder (MONDO_0700092) is emerging but remains limited. In a large screening of 2,999 probands with neurodevelopmental disorders, a single clinically relevant variant affecting a poison exon was identified in SNRPB (PMID:36711854). This variant, although detected in only one case without additional segregation data, suggests that aberrant splicing due to altered poison exon inclusion may contribute to disease risk in a subset of patients. The reported intronic change, likely impairing normal splicing, is consistent with a loss‐of‐function mechanism.

Further supporting evidence comes from functional studies in a related context where SNRPB mutations have been shown to disrupt core spliceosomal activity, leading to abnormal transcript processing (PMID:25504470). However, these functional insights were primarily obtained in the setting of cerebrocostomandibular syndrome and their direct relevance to neurodevelopmental pathology remains to be fully delineated. Overall, while mechanistic data underscore the impact of SNRPB alterations on splicing fidelity, additional genetic and functional studies are required to firmly establish its role in neurodevelopmental disorders. Key take‑home: Even limited genetic signals, when backed by supportive functional disruption, can offer valuable leads for improving diagnostic yield in genomic testing.

References

• bioRxiv • 2023 • Poison exon annotations improve the yield of clinically relevant variants in genomic diagnostic testing PMID:36711854
• Human Mutation • 2015 • Mutations in SNRPB, encoding components of the core splicing machinery, cause cerebro-costo-mandibular syndrome PMID:25504470

Evidence Based Scoring (AI generated)