Why this study matters
Bardet-Biedl syndrome (BBS) is an inherited condition that can affect many parts of the body. Its features may include retinal degeneration and progressive vision loss, obesity, extra fingers or toes (polydactyly), learning or intellectual disability, kidney abnormalities, and differences in genital development. However, no two people with BBS necessarily have the same combination or severity of features.
This clinical variability is closely linked to BBS genetics. More than 20 genes have been associated with the condition, and identifying the responsible gene in an individual or family can be challenging. A 2026 study in Molecular Genetics and Metabolism Reports adds important data from 26 unrelated Iranian patients who were clinically suspected to have BBS. It illustrates both the genetic diversity of BBS and the value of broad genetic testing early in the diagnostic process.
Whole-exome sequencing found relevant variants in every participant
Researchers used whole-exome sequencing (WES), a method that examines the protein-coding portions of thousands of genes at once. This is especially useful for genetically heterogeneous conditions such as BBS, where testing one gene at a time may be slow and may miss the answer.
The study identified causative or potentially causative variants in all 26 participants. These variants were spread across 13 genes, emphasizing that BBS in this cohort did not arise from a single dominant genetic cause.
The genes most often identified were BBS10, BBS2, BBS5, BBS12, and CEP290, each reported in three probands. BBS1 and SDCCAG8 were each found in two probands. Single cases involved BBIP1, BBS7, TTC8, MKS1, IFT172, TRIM32, and GRID2.
This broad distribution has practical implications. A diagnostic strategy focused only on the genes most commonly reported in other populations could overlook families whose BBS is linked to a less frequently detected gene. The findings also expand knowledge of the mutation spectrum in Iranian patients, with pathogenic or likely pathogenic variants particularly prominent in BBS2, BBS5, and BBS10.
Understanding variant classifications
Not every genetic change has the same level of evidence. The researchers classified 15 variants as pathogenic and five as likely pathogenic, meaning available evidence supported a role in disease. Seven were classified as variants of uncertain significance (VUS). A VUS is a DNA change whose health effect is not yet clear; it should not be interpreted in the same way as a confirmed disease-causing variant.
This distinction matters to families. Genetic findings are most useful when they can be interpreted alongside the person’s clinical features, family history, and inheritance pattern. Over time, additional research and data from other families may help clarify whether some uncertain variants contribute to BBS.
Consanguinity and recessive inheritance
All variants identified in this study followed an autosomal recessive pattern. In autosomal recessive conditions, a person generally inherits a non-working copy of the relevant gene from each parent.
Consanguinity was reported in 88.4% of participating families, and the study found a high rate of homozygous variants—changes present in both copies of a gene. This pattern is expected when parents share ancestry and may carry the same rare genetic variant.
For affected families, a molecular diagnosis can support genetic counseling and carrier testing for relatives who may be at risk of having children with BBS. It can also help families understand the genetic explanation for a diagnosis that may otherwise appear unpredictable because BBS features can vary considerably between individuals.
One family, more than one genetic diagnosis
The study also highlights an important reality of comprehensive testing: some individuals may have more than one inherited condition. One participant had BBS-related findings as well as a homozygous pathogenic variant in GJB2, a gene associated with autosomal recessive deafness.
Recognizing a dual diagnosis can be clinically meaningful. It may explain features that do not fit neatly within BBS alone and can help ensure that care planning considers all relevant health needs.
Implications for treatment and future care
This study does not test a new treatment, but it strengthens the foundation needed for more precise care. Establishing the responsible gene can improve diagnostic confidence and help clinicians recognize when a person’s presentation may overlap with other ciliopathies or involve an additional genetic condition.
The authors suggest WES as an effective first-line or early testing approach for clinically suspected BBS and related ciliopathy cases, particularly when appropriate copy-number variant (CNV) analysis is included. CNVs are larger gains or losses of DNA that may not be detected by every genetic testing approach.
As the BBS research landscape develops, detailed genetic information will remain central to targeted diagnostic strategies, carrier screening, and the design of future molecularly informed research. By documenting genetic findings in an Iranian cohort, this work broadens the evidence base beyond any one population and moves the field closer to more equitable, accurate diagnosis for families affected by BBS.