De Novo Variants in the Splicing Factor Gene SF3B1 Are Associated with Neurodevelopmental Disorders - Report - MDSpire
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De Novo Variants in the Splicing Factor Gene SF3B1 Are Associated with Neurodevelopmental Disorders

Constitutional variants in the splicing factor SF3B1 have been linked to neurodevelopmental disorders for the first time, according to a new multinational study co-authored by Phoenix Children’s Pediatric Neurologist and Neurogeneticist Michael Kruer, MD, et al. 

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  • August 14, 2026

  • 2 min

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Clinical Report: De Novo Variants in the Splicing Factor Gene SF3B1

Overview

A multinational study identifies constitutional variants in the SF3B1 gene linked to neurodevelopmental disorders. The cohort of 26 individuals exhibited global developmental delay and distinct phenotypic features, with variants primarily arising de novo.

Background

The identification of constitutional variants in SF3B1 expands the understanding of genetic factors contributing to neurodevelopmental disorders. SF3B1 plays a role in pre-mRNA splicing, and its dysfunction may lead to various developmental and syndromic presentations.

Data Highlights

Variant TypeNumber of Cases
Loss-of-function9
Missense17

Key Findings

  • Constitutional variants in SF3B1 are associated with neurodevelopmental disorders for the first time.
  • The cohort included 26 individuals with global developmental delay and variable neurologic features.
  • Variants were primarily de novo, with 9 loss-of-function and 17 missense variants identified.
  • Missense variants were linked to a more severe, syndromic phenotype, including cardiac and gastrointestinal anomalies.
  • Functional assays showed that missense variants did not cause complete loss of SF3B1 function but altered splicing across many transcripts.

Clinical Implications

Clinicians should consider SF3B1 variants in the differential diagnosis of children presenting with developmental delays or syndromic features.

Conclusion

The study establishes a link between SF3B1 variants and neurodevelopmental disorders.

Related Resources & Content

  1. Bernard DG, et al., Nature Communications, 2026 -- De novo variants in the splicing factor gene SF3B1 are associated with neurodevelopmental disorders
  2. Brain — Deep learning analyses of splicing variants identify the link of PCP4 with amyotrophic lateral sclerosis
  3. Brain — De novo and inherited variants in DDX39B cause a novel neurodevelopmental syndrome
  4. Frontiers in Pediatrics — A homozygous splice-site variant in SAMHD1 shows variable expressivity of Aicardi-Goutières Syndrome Type 5: a case report and literature review
  5. Brain — De novo variants disrupt an LDB1-regulated transcriptional network in congenital ventriculomegaly
  6. Deep learning analyses of splicing variants identify the link of PCP4 with amyotrophic lateral sclerosis
  7. De novo and inherited variants in DDX39B cause a novel neurodevelopmental syndrome
  8. A homozygous splice-site variant in SAMHD1 shows variable expressivity of Aicardi-Goutières Syndrome Type 5: a case report and literature review
  9. Heterozygous pathogenic variants in the splicing factor SF1 lead to a large spectrum of neurodevelopmental disorders
  10. Genetic Evaluation of the Child With Intellectual Disability or Global Developmental Delay: Clinical Report
  11. De novo variants in the splicing factor gene SF3B1 are associated with neurodevelopmental disorders | Nature Communications

Original Source(s)

De Novo Variants in the Splicing Factor Gene SF3B1 Are Associated with Neurodevelopmental Disorders

  • by

  • August 14, 2026

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