Introduction: Bardet-Biedl Syndrome is a rare autosomal recessive disorder characterized by multisystem manifestations, such as early-onset obesity, hypogonadotropic hypogonadism, retinal dystrophy, polydactyly, renal anomalies and intellectual disability. Phenotypic variability makes diagnosis challenging. Central obesity and hypogonadotropic hypogonadism are frequently observed, but often overlooked. Case: We report a 12-year-old male who was referred at the age of 10 years for evaluation of central obesity and buried penis. He was born at term with birth weight of 3,200 g. Both parents were non-consanguineous, and antenatal history was unremarkable. Early-onset excessive weight gain was noted from infancy, with hyperphagia during early childhood. His weight remained persistently above the 95th centile, and height around the 90th centile, slightly exceeding midparental height expectations. Buried penis was identified at birth. Polydactyly is absent. He also demonstrates learning difficulties. Early diagnostic considerations include Klinefelter syndrome due to buried penis, and PraderWilli Syndrome due to central obesity with co-existence of learning difficulties. Further evaluation excluded PraderWilli Syndrome, and conventional karyotyping ruled out Klinefelter syndrome. Clinical assessment revealed prepubertal Tanner stage, bilaterally palpable testes (3 mL), and a stretched penile length <2 cm. Endocrine evaluation demonstrated a prepubertal response to LHRH stimulation, and poor testosterone response to hCG, suggesting hypogonadotropic hypogonadism with poor Leydig cell function. Whole exome sequencing confirmed a BBS2 gene mutation, establishing the diagnosis of Bardet-Biedl Syndrome. This mutation disrupts hypothalamic signaling, leading to the multisystem involvement observed. Over the follow-up period, he reported difficulty with night vision. Conclusion Not all syndromic obesity is immediately apparent— Bardet-Biedl Syndrome should be considered even in the absence of classical features. Marked phenotypic variability often leads to delayed diagnosis, highlighting the need for vigilant clinical suspicion and prompt genetic study to ensure timely recognition. Early recognition is critical, as endocrine and other associated complications can significantly impact long-term health.
Bardet-Biedl Syndrome ; Obesity

OBJECTIVE: To carry out genetic testing on two fetuses with prenatal ultrasound finding of polydactyly and renal abnormalities to determine the underlying causes. METHODS: Two fetuses with structural abnormalities detected by prenatal ultrasound at Cangzhou People's Hospital in 2021 were selected as the study subjects. Genomic DNA was extracted from the muscle tissue of the abortus and peripheral blood samples from both parents. Whole-exome sequencing (WES) was conducted on the trio to detect the genetic variants. Quantitative PCR was used to validate the exonic deletions. This study has been approved by the Ethics Committee of Cangzhou People's Hospital (Ethics No.K2020-049). RESULTS: Prenatal ultrasound revealed postaxial polydactylies of fingers and toes and slightly enlarged kidneys with increased echogenicity in fetus 1, along with polydactyly of both hands, enlarged kidneys, and enhanced echogenicity of renal parenchyma in fetus 2. Trio-WES analysis revealed that fetus 1 has harbored a pathogenic c.1339G>A variant of the BBS1 gene, along with a heterozygous 426 bp deletion in the 11q13.2 region, which was unreported previously. The deletion has involved exons 10 and 11 of the BBS1 gene. The two variants were inherited from its mother and father, respectively. Fetus 2 was found to harbor a pathogenic c.539G>A variant and a likely pathogenic c.49G>A variant of the BBS10 gene, which were inherited from its mother and father, respectively. The c.49G>A variant has not been documented in databases and the literature. CONCLUSION Two rare fetuses with Bardet-Biedl syndrome have been diagnosed. Above finding has expanded the mutational spectrum of this syndrome and has important implications for genetic counseling for the affected families.
Humans ; Bardet-Biedl Syndrome/diagnostic imaging* ; Female ; Pregnancy ; Fetus/abnormalities* ; Ultrasonography, Prenatal ; Phenotype ; Polydactyly/diagnostic imaging* ; Exome Sequencing ; Adult ; Genetic Testing ; Male ; Prenatal Diagnosis ; Group II Chaperonins/genetics* ; Microtubule-Associated Proteins

No abstract available.
Bardet-Biedl Syndrome ; Humans ; Retinitis Pigmentosa ; Retinitis

BACKGROUND: Because of genetically and phenotypically heterogenous features, identification of causative genes for inherited retinal diseases (IRD) is essential for diagnosis and treatment in coming gene therapy era. To date, there are no large-scale data of the genes responsible for IRD in Korea. The aim of this study was to identify the distribution of genetic defects in IRD patients in Korea. METHODS: Medical records and DNA samples from 86 clinically diagnosed IRD patients were consecutively collected between July 2011 and May 2015. We applied the next-generation sequencing strategy (gene panel) for screening 204 known pathogenic genes associated with IRD. RESULTS: Molecular diagnoses were made in 38/86 (44.2%) IRD patients: 18/44 (40.9%) retinitis pigmentosa (RP), 8/22 (36.4%) cone dystrophy, 6/7 (85.7%) Stargardt disease, 1/1 (100%) Best disease, 1/1 (100%) Bardet-Biedl syndrome, 1/1 (100%) congenital stationary night blindness, 1/1 (100%) choroideremia, and 2/8 (25%) other macular dystrophies. ABCA4 was the most common causative gene associated with IRD and was responsible for causing Stargardt disease (n = 6), RP (n = 1), and cone dystrophy (n = 1). In particular, mutations in EYS were found in 4 of 14 autosomal recessive RP (29%). All cases of Stargardt disease had a mutation in the ABCA4 gene with an autosomal recessive trait. CONCLUSION: This study provided the distribution of genetic mutations responsible for causing IRD in the Korean patients. This data will serve as a reference for future genetic screening and treatment for Korean IRD patients.
Bardet-Biedl Syndrome ; Choroideremia ; Diagnosis ; DNA ; Genetic Testing ; Genetic Therapy ; Humans ; Korea ; Macular Degeneration ; Mass Screening ; Medical Records ; Night Blindness ; Retinal Diseases ; Retinaldehyde ; Retinitis Pigmentosa ; Vitelliform Macular Dystrophy

Cilia and flagella on eukaryotic cells are polarized organelles extending from the surfaces of cells, which participate not only in cell motility, but also in signal transduction and other processes. Structural or functional abnormalities of cilia can cause various human diseases, termed ciliopathies. Bardet-Biedl syndrome (BBS) is a ciliopathic human genetic disorder, and the pathogenesis is that mutated BBS genes result in abnormal cilia function. In order to study the pathogenic genes BBS8, we screened bbs8 mutant in Chlamydomonas reinhardtii and did a lot of physiology and biochemistry experiments. We affirmed that BBS8 protein was a cilia protein and had specific localization in the basal body by immunofluorescence (IF). The bbs8 mutant lost photokinesis, and it was defective in flagella shortening with drug induction. The results of silver staining and mass spectrometric analysis showed aberrant accumulation of flagellar proteins in the mutant flagella. We concluded that the BBS8 protein plays a significant role in flagellar membrane proteins transport, and the BBS8 protein might mediate retrograde transport to exert physiological function in the process.
Bardet-Biedl Syndrome ; Chlamydomonas reinhardtii ; Cilia ; Flagella ; Humans ; Protein Transport

Bardet-Biedl syndrome (BBS) is a rare genetic disease caused by ciliary structure abnormality or dysfunction. To date, more than 21 BBS genes (BBS1 - 21) have been reported to independently cause the disorder. Although the cellular functions of BBS proteins are not yet fully understood, model organisms have revealed that such proteins are involved in ciliary functions and intracellular transport. Among the 21 BBS genes, BBS7 is unique in that its product is a subunit of the BBSome and can directly interact with the BBS chaperonin complex. Previous studies using animal models showed that BBS7 mutation can cause similar phenotypes to human patients, and human disease caused by BBS7 variants are special and more complex. This article reviewed recent progresses on BBS7.
Animals ; Bardet-Biedl Syndrome ; genetics ; Humans ; Mutation ; Proteins ; genetics

Obesity has become a common healthcare problem worldwide. Cilia are tiny hair-like organelles on the cell surface that are generated and anchored by the basal body. Non-motile primary cilia have been considered to be evolutionary rudiments until a few decades, but they are now considered as important signaling organelles because many receptors, channels, and signaling molecules are highly expressed in primary cilia. A potential role of primary cilia in metabolic regulation and body weight maintenance has been suspected based on rare genetic disorders termed as ciliopathy, such as Bardet-Biedl syndrome and Alström syndrome, which manifest as obesity. Recent studies have demonstrated involvement of cilia-related cellular signaling pathways in transducing metabolic information in hypothalamic neurons and in determining cellular fate during adipose tissue development. In this review, we summarize the current knowledge about cilia and cilia-associated signaling pathways in the regulation of body metabolism.
Adipose Tissue ; Alstrom Syndrome ; Bardet-Biedl Syndrome ; Basal Bodies ; Body Weight Maintenance ; Cilia* ; Delivery of Health Care ; Energy Metabolism* ; Hedgehogs ; Metabolism ; Neurons ; Obesity ; Organelles ; Wnt Signaling Pathway

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disease characterized by retinopathy, obesity, and polydactyly. So far 21 candidate genes have been discovered, and mutations of such genes can all cause the BBS phenotype. As one of the main features of the disease, the obesity in BBS has been associated with leptin resistance and abnormal adipogenesis. However, its molecular etiology is not yet completely clear. Here the molecular mechanism of BBS-associated obesity is reviewed.
Bardet-Biedl Syndrome ; genetics ; Humans ; Obesity ; genetics ; Phenotype ; Polydactyly ; genetics

BACKGROUND: Alstrom syndrome and Bardet-Biedl syndrome are autosomal recessively inherited ciliopathies with common characteristics of obesity, diabetes, and blindness. Alstrom syndrome is caused by a mutation in the ALMS1 gene, and Bardet-Biedl syndrome is caused by mutations in BBS1-16 genes. Herein we report genetically confirmed cases of Alstrom syndrome and Bardet-Biedl syndrome in Korea using whole exome sequencing. METHODS: Exome capture was done using SureSelect Human All Exon Kit V4+UTRs (Agilent Technologies). HiSeq2000 system (Illumina) was used for massive parallel sequencing. Sanger sequencing was used for genotype confirmation and familial cosegregation analysis. RESULTS: A 21-year old Korean woman was clinically diagnosed with Alstrom syndrome. She had diabetes, blindness, obesity, severe insulin resistance, and hearing loss. Whole exome sequencing revealed a nonsense mutation in exon 10 of ALMS1 (c.8776C>T, p.R2926X) and a seven base-pair deletion resulting in frameshift mutation in exon 8 (c.6410_6416del, p.2137_2139del). A 24-year-old Korean man had Bardet-Biedl syndrome with diabetes, blindness, obesity, and a history of polydactyly. Whole exome sequencing revealed a nonsynonymous mutation in exon 11 of the BBS1 gene (c.1061A>G, p.E354G) and mutation at the normal splicing recognition site of exon 7 of the BBS1 gene (c.519-1G>T). CONCLUSION: We found novel compound heterozygous mutations of Alstrom syndrome and Bardet-Biedl syndrome using whole exome sequencing. The whole exome sequencing successfully identified novel genetic variants of ciliopathy-associated diabetes.
Alstrom Syndrome ; Bardet-Biedl Syndrome ; Blindness ; Codon, Nonsense ; Diabetes Mellitus ; Exome* ; Exons ; Female ; Frameshift Mutation ; Genotype ; Hearing Loss ; Humans ; Insulin Resistance ; Korea ; Obesity ; Obesity, Morbid ; Polydactyly ; Young Adult

No abstract available.
Adult ; Alleles ; Asian Continental Ancestry Group/*genetics ; Bardet-Biedl Syndrome/diagnosis/*genetics ; Base Sequence ; Blindness/pathology ; DNA/chemistry/metabolism ; Exons ; *Heterozygote ; Humans ; Macular Degeneration/diagnosis ; Male ; *Mutation ; Pedigree ; Phenotype ; Polymorphism, Single Nucleotide ; Proteins/*genetics ; Republic of Korea