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B9D1 – Meckel syndrome

Three unrelated probands from targeted exon-enriched sequencing exhibited biallelic B9D1 variants including a nonsense c.391C>T (p.Gln131Ter), a missense c.181C>T (p.Arg61Trp), and a splice-donor c.341+2T>C with exon 4 deletion (PMID:21493627). A fourth prenatal case carried homozygous c.151T>C (p.Ser51Pro) (PMID:40565534). Affected fetuses uniformly showed occipital encephalocele, polycystic kidney dysplasia, postaxial polydactyly, and hepatic fibrosis consistent with autosomal recessive inheritance.

Functional assays demonstrate markedly reduced ciliogenesis in patient fibroblasts (PMID:21493627), and B9d1⁻/⁻ mice recapitulate key MKS features including polydactyly and kidney cysts with disrupted Hedgehog signaling (PMID:21763481). These combined genetic and experimental data support a Limited clinical validity classification for B9D1 in Meckel syndrome. Key take-home: inclusion of B9D1 in MKS diagnostic panels enhances prenatal diagnosis and genetic counseling.

References

  • Human molecular genetics • 2011 • B9D1 is revealed as a novel Meckel syndrome (MKS) gene by targeted exon-enriched next-generation sequencing and deletion analysis. PMID:21493627
  • American journal of human genetics • 2011 • Disruption of a ciliary B9 protein complex causes Meckel syndrome. PMID:21763481
  • Genes • 2025 • Investigating the Role of B9D1 in Meckel-Gruber Syndrome: A Case Report and Comprehensive Literature Review. PMID:40565534

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

4 unrelated probands with biallelic B9D1 variants in MKS context

Genetic Evidence

Limited

Four probands with biallelic LoF and rare missense variants in B9D1 under autosomal recessive inheritance ([PMID:21493627], [PMID:40565534])

Functional Evidence

Moderate

Patient cell immunofluorescence and B9d1 knockout mouse models demonstrate compromised ciliogenesis and recapitulate MKS phenotypes ([PMID:21493627], [PMID:21763481])