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Bardet−Biedl Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Besides BBS, gene mutations that lead to ciliary dysfunction are also implicated in other ciliopathies. For example, genetic changes involving BBS14 (CEP290) can also cause Joubert syndrome, Leber congenital amaurosis, Meckel syndrome, and Senior−Loken syndrome (Table 25.1). In addition, BBS may overlap clinically to other syndromes with distinct gene defects (e.g., Alström syndrome containing ALMS1 mutations, and Joubert syndrome containing NPHP1 gene mutations) [13].
Approaches to Studying Polycystic Kidney Disease in Zebrafish
Published in Jinghua Hu, Yong Yu, Polycystic Kidney Disease, 2019
Besides ADPKD and ARPKD, there are some other genetic diseases or ciliopathies that manifest polycystic kidney syndrome. Ciliopathies refer to the diseases caused by structural or functional defects in cilia, the hair-like subcellular organelles. Polycystin-1 (PC1) and polycystin-2 (PC2), two proteins encoded by PKD1 and PKD2, respectively, form complexes and are transported to the cilia.6,7 The ciliary trafficking of the PC1 and PC2 complex are important for their in vivo function.8,9 Thus, ADPKD is considered as one of the most common ciliopathies. Other ciliopathies with PKD phenotype include nephronophthisis (NPHP), Joubert syndrome and related disorders (JSRD), Meckel syndrome (MKS), Bardet–Biedl syndrome (BBS), oral-facial-digital syndrome (OFD), et al.10 Most PKD will progress to end-stage renal disease around the age of 60. So far, there is no effective treatment except renal transplantation. Thus, it's important to understand the pathogenesis of PKD.
Renal and urinary tract diseases
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
Juvenile nephronophthisis is an autosomal recessive disease that has early onset and will often lead to end-stage renal failure in childhood. It is autosomal recessive in inheritance and is often accompanied by non-renal features, such as features of a more generalised ciliopathy as in Jeune's asphyxiating thoracic dystrophy, Joubert syndrome (with cerebellar hypoplasia), Bardet-Biedl syndrome (with polydactyly and obesity) or Meckel-Gruber syndrome (with malformation of the central nervous system, notably occipital encephalocoele and polydactyly). The ciliopathies comprise a varied group of disorders that share many features but also show great locus heterogeneity. They have been a focus of some very productive research into disease mechanisms in embryogenesis.
Meckel Gruber and Joubert Syndrome Diagnosed Prenatally: Allelism between the Two Ciliopathies, Complexities of Mutation Types and Digenic Inheritance
Published in Fetal and Pediatric Pathology, 2022
Somya Srivastava, Rani Manisha, Aradhana Dwivedi, Harshita Agarwal, Deepti Saxena, Vinita Agrawal, Kausik Mandal
Ciliopathies are a diverse group of disorders which occur due to dysfunction of motile or immotile cilia. They have 2 important functions-motility and cell signaling. Impaired ciliary motility exclusively results in primary ciliary dyskinesia which gives rise to disorders encompassing infertility, situs inversus, bronchiectasis and atelectasis. Impaired signaling and sensory function of motile or immotile cilia results in disorders of multiple organs (brain, eye, ear, kidney, liver, nose, skeleton). Ciliogenesis starts from a mother centriole which matures into a basal body, docks on the plasma membrane and further gives rise to the ciliary shaft. In between the shaft and the basal body lies the transition zone which controls the trafficking of molecules into and out of the cell [1].
Retinal dystrophy as part of TTC21B-associated ciliopathy
Published in Ophthalmic Genetics, 2021
Tamar Ben-Yosef, Nurit Asia Batsir, Tahleel Ali Nasser, Miriam Ehrenberg
Ciliopathies are a group of inherited diseases caused by mutations in genes associated with the structure and function of primary cilia. Primary cilia function as signaling hubs that sense environmental cues and are pivotal for organ development and function, and for tissue homeostasis. By their nature, cilia defects are usually pleiotropic, affecting more than one system (1). Organs that are commonly affected in ciliopathies are the central nervous system, kidney, liver, pancreas, skeletal system, inner ear, and retina. In the retina, photoreceptor outer segments are highly modified primary sensory cilia. The proximal end of the outer segment is linked to the cell body (i.e. the inner segment) via a connecting cilium which is structurally homologous to the transition zone of primary cilia (2). Consequently, retinal pathogenesis is a common finding in ciliopathies. Some examples of the better-known ciliopathies associated with retinal dystrophies (RD) are Bardet-Biedel Syndrome (3), Usher Syndrome (4), Joubert Syndrome, (5) and Senior-Loken Syndrome (6).
The spermatogenesis-associated protein-7 (SPATA7) gene – an overview
Published in Ophthalmic Genetics, 2020
The SPATA7 gene encodes a protein that is present in the photoreceptor axoneme, and there are about 20 other genes coding for axonemal proteins, such as the Bardet-Biedl syndrome (BBS) loci. The large number of genes that constitute even this sub-group of ciliary protein genes are associated with several forms of ciliopathies that are phenotypically very diverse. Apart from the heterogeneity, there may be an overlap in clinical manifestations between different genetic forms of ciliopathies, thus complicating any attempts at genotype-phenotype correlation (21). BBS manifests with infertility in the form of hypogonadism (more common in males), along with retinopathy, obesity, polydactyly, and renal defects. Although the SPATA7 gene is expressed in spermatocytes, there is no evidence of infertility in either Spata7 −/- mice which were observed to be viable, fertile, and without any gross changes in morphology (22,23). Among patients with retinal disease, one patient with SPATA7 mutations was noted to have infertility (12), but this is not apparently a frequent association in these patients.