Bardet-Biedl Syndrome-Multiple Kaleidoscope Images: Insight into Mechanisms of Genotype-Phenotype Correlations.

Bardet-Biedl Syndrome is a rare non-motile primary ciliopathy with multisystem involvement and autosomal recessive inheritance. The clinical picture is extremely polymorphic. The main clinical features are retinal cone-rod dystrophy, central obesity, postaxial polydactyly, cognitive impairment, hypogonadism and genitourinary abnormalities, and kidney disease. It is caused by various types of mutations, mainly in genes encoding BBSome proteins, chaperonins, and IFT complex. Variable expressivity and pleiotropy are correlated with the existence of multiple genes and variants modifiers. This review is focused on the phenomena of heterogeneity (locus, allelic, mutational, and clinical) in Bardet-Biedl Syndrome, its mechanisms, and importance in early diagnosis and proper management.

Deletion in the Bardet-Biedl Syndrome Gene TTC8 Results in a Syndromic Retinal Degeneration in Dogs.

In golden retriever dogs, a 1 bp deletion in the canine TTC8 gene has been shown to cause progressive retinal atrophy (PRA), the canine equivalent of retinitis pigmentosa. In humans, TTC8 is also implicated in Bardet-Biedl syndrome (BBS). To investigate if the affected dogs only exhibit a non-syndromic PRA or develop a syndromic ciliopathy similar to human BBS, we recruited 10 affected dogs to the study. The progression of PRA for two of the dogs was followed for 2 years, and a rigorous clinical characterization allowed a careful comparison with primary and secondary characteristics of human BBS. In addition to PRA, the dogs showed a spectrum of clinical and morphological signs similar to primary and secondary characteristics of human BBS patients, such as obesity, renal anomalies, sperm defects, and anosmia. We used Oxford Nanopore long-read cDNA sequencing to characterize retinal full-length TTC8 transcripts in affected and non-affected dogs, the results of which suggest that three isoforms are transcribed in the retina, and the 1 bp deletion is a loss-of-function mutation, resulting in a canine form of Bardet-Biedl syndrome with heterogeneous clinical signs.

Establishing a connection between cilia and Bardet-Biedl Syndrome.

Bardet-Biedl Syndrome (BBS) is a gentic disorder with primary features of retinal dystrophy, obesity, polydactyly, structural and functional renal abnormalities, and learning disabilities. In addition to displaying remarkable pleiotropy, BBS is a heterogeneous disorder with linkage to at least eight loci. The identification of the first five BBS genes provided little insight into BBS protein function. Ansley at al. have now identified a sixth BBS gene (BBS8) and provide evidence that the BBS8 protein and other BBS proteins localize to the basal body of ciliated cells, suggesting that BBS is a ciliary dysfunction disorder.

Bardet-Biedl syndrome.

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy characterised by retinal dystrophy, obesity, post-axial polydactyly, renal dysfunction, learning difficulties and hypogonadism. Many associated minor features can be helpful in making a diagnosis and are important in the clinical management of BBS. The diagnosis is based on clinical findings and can be confirmed by sequencing of known disease-causing genes in 80% of patients. BBS genes encode proteins that localise to the cilia and basal body and are involved in cilia biogenesis and function. Mutations lead to defective cilia accounting in part for the pleiotropic effects observed in BBS. We provide an overview of BBS including the clinical findings, current understanding of cilia biology, and a practical approach to diagnosis, genetic counselling and up-to-date management.

Síndrome de bardet-bieldet: reporte de un caso / Bardet-Biedl's síndrome: a case report

Se presentan los hallazgos clínicos y de laboratorio de un paciente con síndrome de Bardet-Biedl. Los primeros síntomas aparecieron durante la adolescencia lo cual admite un modo de herencia autonómica recesiva. Al examen físico se constató polidactilia axial de manos y pies, retinosis pigmentaria, obesidad troncular, retraso mental e hipogonadismo, también se encontró diabetes mellitus no insulino dependiente, hipertensión arterial e insuficiencia renal crónica terminal. Se concluyó que esta enfermedad de inicio temprano en la vida puede causar ceguera en la adolescencia y fallo renal crónico en la edad adulta

Síndrome de bardet-biedl asociado a síndrome antifosfolipidico / Syndrome of bardet-buedl association a antiphospholipid syndrome

El síndrome de Bardet-Biedl se caracteriza por la presenica de retinopatía, obesidad, polidactilia, hipogonadismo y daño renal variable. Hasta ahora no se había reportado su asociación con síndrome Antifosfolipídico. Caso clínico: adolescente masculino de 15 años con retinitis pigmentaria e insuficiencia renal crónica. La biopsia renal reveló: obsolescencia glomerular marcada con fibrosis intersticial severa. Evaluación inmunológica normal, cariotipo 46, XY, ruptura de cromátidas en autosomas, 1p, 2p, 9p, 14q, 15q. Se diagnóstico Síndrome de Bardet-Biedl. Se inició hemodiálisis con corta duración de accesos vasculares. Al año recibió trasplante renal de cadáver con disfunción temprana del injerto. A los 26 días, se realizó trasplantectomía por trombosis arterial y venosa renal. El ecodoppler reportó trombosis venosa profunda. Se realizaron pruebas hematológicas: anticoagulante lúpico: LA1 149 seg LA2 147 seg (VN: 0-45), anticardiolipina: IgG 80 GPL/ml (VN:<10), IgM<7 MPL/ml. (normal). Se inició tratamiento con enoxaparina y warfarina, con mejoría del proceso trombólico