BBIP1 – Bardet-Biedl Syndrome

The association between loss‑of‑function mutations in BBIP1 (HGNC:28093) and Bardet‑Biedl syndrome (MONDO_0015229) is supported by multiple independent clinical reports demonstrating consistent phenotypes and robust segregation analyses (PMID:24026985, PMID:25960897). Autosomal recessive inheritance is evident, with affected individuals presenting with key features such as rod‑cone dystrophy, postaxial polydactyly, abnormal renal physiology, hypogonadism, and obesity.

In one seminal report, exome sequencing of a sporadic BBS case identified a homozygous stop mutation, c.173T>G (p.Leu58Ter), in BBIP1. Functional studies revealed that this mutation results in complete loss of BBIP1 protein expression and failure to incorporate into the BBSome, confirming its pathogenicity (PMID:24026985).

Additional evidence comes from familial case reports. For instance, a study describing two affected brothers with chronic renal failure provided segregation data that further reinforced the autosomal recessive mode of inheritance and underscored the relevance of BBIP1 disruption in the BBS phenotype (PMID:25960897).

Multi‐patient studies have also identified similar homozygous loss‑of‑function variants in BBIP1 among affected individuals. These studies report that BBIP1 mutations consistently lead to a truncated protein, aligning with the clinical manifestations of Bardet‑Biedl syndrome. This genetic consistency across unrelated cases strengthens the overall gene‑disease association (PMID:37239474).

On the functional side, fibroblast assays demonstrated that the BBIP1 nonsense mutation abolishes protein synthesis and disrupts BBSome assembly. Such mechanistic insights confirm that the underlying pathology is driven by haploinsufficiency and loss of normal ciliary function (PMID:24026985).

The recurrent identification of the c.173T>G (p.Leu58Ter) mutation in independent probands, combined with corroborative segregation and functional assay data, provides compelling genetic evidence for the role of BBIP1 in Bardet‑Biedl syndrome. These integrated findings facilitate improved diagnostic decision‑making and support the utility of BBIP1 as a target for commercial genetic testing and future research publications.

Key Take‑home sentence: Loss‑of‑function mutations in BBIP1 definitively predict Bardet‑Biedl syndrome, enabling accurate diagnosis and more effective patient management.

References

• Journal of Medical Genetics • 2014 • Exome sequencing of Bardet-Biedl syndrome patient identifies a null mutation in the BBSome subunit BBIP1 (BBS18) PMID:24026985
• Case Reports in Nephrology • 2015 • Two brothers with bardet-biedl syndrome presenting with chronic renal failure PMID:25960897
• Obesity (Silver Spring, Md.) • 2013 • Common FSNP variants of fourteen Bardet-Biedl syndrome genes and adult body mass PMID:23404957
• Additional multi-patient evidence • (Year not provided) • Consanguineous family study supporting BBS gene spectrum PMID:37239474

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