The Experts below are selected from a list of 2919 Experts worldwide ranked by ideXlab platform
Tarun Sharma - One of the best experts on this subject based on the ideXlab platform.
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Ciliopathy: Alström Syndrome
Advances in experimental medicine and biology, 2018Co-Authors: Stephen H. Tsang, Alicia R P Aycinena, Tarun SharmaAbstract:Alstrom syndrome is an autosomal recessive disease with multisystem involvement, including cone-rod dystrophy, hearing loss, type 2 diabetes, insulin resistance with hyperinsulinemia, dilated cardiomyopathy, and progressive hepatic and renal failure. Patients present in childhood with photophobia and nystagmus, and mimic Leber congenital amaurosis (LCA). The fundus shows pigmentary retinopathy with peau d'orange appearance and some fine white dots like drusen around the macula; the disc is pale, with attenuated retinal vessels (Fig. 35.1). Patients have short stature; boys have hypogonadotropic hypogonadism and girls have polycystic ovary syndrome (PCOS). Obesity is always present, with markedly increased triglyceride and VLDL-C levels; arterial hypertension is diagnosed as early as 2 years of age. There is no polydactyly or syndactyly. About half have developmental delay, but intelligence is usually normal.
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Ciliopathy usher syndrome
Advances in Experimental Medicine and Biology, 2018Co-Authors: Alicia R P Aycinena, S Tsang, Tarun SharmaAbstract:Ciliopathies are a group of disorders caused by a defect in ciliogenesis, ciliary protein trafficking. Because nearly every cell in the body (including the photoreceptors) contains cilia, defects in ciliary proteins typically affect multiple organ systems. Usher syndrome is the most common syndromic cause of retinitis pigmentosa (RP) and accounts for 10–20% of cases of RP Inheritance is autosomal recessive, and the retinal dystrophy is usually rod-cone dystrophy (Figs. 32.1 and 32.2). These patients have RP with sensorineural hearing loss (partial or complete) since birth; some may have vestibular dysfunction. Most patients retain central vision of about 20/40 until about age 40. Usher Syndrome 1 (USH1): Profound congenital sensorineural hearing loss on audiometry, absent vestibular function, and typical RP (onset by 10 years of age); accounts for about 70% of all Usher cases. Patient may benefit from a cochlear implant. The retinitis pigmentosa occurs at an early age (childhood onset) and progress slowly. Usher Syndrome 2 (USH2): Moderate to severe congenital sensorineural hearing loss on audiometry (predominantly for higher frequencies), normal vestibular function, and typical RP (onset by 20 years of age); accounts for about 26% of all Usher cases. Usher Syndrome 3 (USH3): Progressive sensorineural hearing loss and typical RP (onset in second decade); accounts for about 4% of all Usher cases. Vestibular function is normal in about half of patients, but abnormal in the other half.
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Ciliopathy bardet biedl syndrome
Advances in Experimental Medicine and Biology, 2018Co-Authors: Alicia R P Aycinena, S Tsang, Tarun SharmaAbstract:Bardet-Biedl syndrome (BBS) is an autosomal recessive disease with a prevalence of about 1/125,000. The syndrome involves mixed rod-cone dystrophy (which becomes obvious by 6 years of age). About two thirds of patients have postaxial polydactyly, and sometimes syndactyly, brachydactyly, and/or clinodactyly may be present. Hypogonadism and renal involvement occur in about 40%, mental retardation in about 50%, and truncal obesity in about 70%; it is present early, along with insulin resistance, type 2 diabetes, dyslipidemia, and hypertension. Vision becomes markedly impaired by about age 30 years. The BBS is genetically heterogeneous entity with considerable phenotypic variability. Other associated problems include CNS-related ataxia, abnormal gait, and facial hypotonia, as well as anomalies such as high palate, hearing loss, and cardiac malformations. In males, there is oligospermia, leading to infertility. Around 50–80% of BBS patients have renal malformations (like cyst, agenesis or scarring) and renal dysfunction leading to end-stage renal disease. There are no pigmentary changes before the age of 1–2 years. Later, subtle pigmentary changes appear in the macula or peripapillary area. Several years later, pigments appear in the equatorial region, along with attenuation of retinal blood vessels and waxy pallor of the optic disc. Eventually, the macula may show atrophic changes (Figs. 33.1, 33.2 and 33.3). Electroretinography (ERG) shows involvement of rods and cones and is abnormal even before the fundus shows changes. A perimacular hyperfluorescent ring can be seen.
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Ciliopathy senior loken syndrome
Advances in Experimental Medicine and Biology, 2018Co-Authors: Alicia R P Aycinena, Stephen H. Tsang, Tarun SharmaAbstract:Senior-Loken syndrome is a rare autosomal recessive disease with a prevalence of 1:1,000,000. Retinopathy may progress as Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), or sector RP (Figs. 34.1 and 34.2). Onset of photophobia, nystagmus, and hyperopia can occur in the first few years of life or later in childhood. Patients experience nephronophthisis, characterized by cystic kidney disease (medullary cystic kidney disease), reduced concentrating ability, and chronic tubulointerstitial nephritis, which progresses to end-stage renal disease. Hypertension is common.
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Ciliopathy sjogren larsson syndrome
Advances in Experimental Medicine and Biology, 2018Co-Authors: Alicia R P Aycinena, Stephen H. Tsang, Tarun SharmaAbstract:Glistening yellow-white crystalline inclusions in foveal and parafoveal areas are almost pathognomonic (Fig. 36.1). These inclusions are evident at 1-2 years old and increase with age. Patients may have corneal stromal opacities, punctate keratitis, myopia, and astigmatism. About 50% have pigmentary degeneration of the retina, with decreased visual acuity and marked photophobia. Patients have dry, scaly skin (ichthyosis). Affected infants tend to be born prematurely. They also have neurological problems due to leukoencephalopathy (affecting the white matter of the brain). Intellectual disability varies from mild to severe, along with dysarthria and delayed speech.
Stephen H. Tsang - One of the best experts on this subject based on the ideXlab platform.
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comparison of structural progression between Ciliopathy and non Ciliopathy associated with autosomal recessive retinitis pigmentosa
Orphanet Journal of Rare Diseases, 2019Co-Authors: Vitor K L Takahashi, Julia T Takiuti, Mary Ben L Apatoff, Jimmy Duong, Vinit B Mahajan, Stephen H. TsangAbstract:To evaluate and compare the progression of Ciliopathy and non-Ciliopathy autosomal recessive Retinitis Pigmentosa patients (arRP) by measuring the constriction of hyperautofluorescent rings in fundus autofluorescence (FAF) images and the progressive shortening of the ellipsoid zone line width obtained by spectral-domain optical coherence tomography (SD-OCT). For the Ciliopathy group, the estimated mean shortening of the ellipsoid zone line was 259 μm per year and the ring area decreased at a rate of 2.46 mm2 per year. For the non-Ciliopathy group, the estimated mean shortening of the ellipsoid zone line was 84 μm per year and the ring area decreased at a rate of 0.7 mm2 per year. Our study was able to quantify and compare the loss of EZ line width and short-wavelength autofluorescence (SW-AF) ring constriction progression over time for Ciliopathy and non-Ciliopathy arRP genes. These results may serve as a basis for modeling RP disease progression, and furthermore, they could potentially be used as endpoints in clinical trials seeking to promote cone and rod survival in RP patients.
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Ciliopathy: Alström Syndrome
Advances in experimental medicine and biology, 2018Co-Authors: Stephen H. Tsang, Alicia R P Aycinena, Tarun SharmaAbstract:Alstrom syndrome is an autosomal recessive disease with multisystem involvement, including cone-rod dystrophy, hearing loss, type 2 diabetes, insulin resistance with hyperinsulinemia, dilated cardiomyopathy, and progressive hepatic and renal failure. Patients present in childhood with photophobia and nystagmus, and mimic Leber congenital amaurosis (LCA). The fundus shows pigmentary retinopathy with peau d'orange appearance and some fine white dots like drusen around the macula; the disc is pale, with attenuated retinal vessels (Fig. 35.1). Patients have short stature; boys have hypogonadotropic hypogonadism and girls have polycystic ovary syndrome (PCOS). Obesity is always present, with markedly increased triglyceride and VLDL-C levels; arterial hypertension is diagnosed as early as 2 years of age. There is no polydactyly or syndactyly. About half have developmental delay, but intelligence is usually normal.
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Ciliopathy senior loken syndrome
Advances in Experimental Medicine and Biology, 2018Co-Authors: Alicia R P Aycinena, Stephen H. Tsang, Tarun SharmaAbstract:Senior-Loken syndrome is a rare autosomal recessive disease with a prevalence of 1:1,000,000. Retinopathy may progress as Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), or sector RP (Figs. 34.1 and 34.2). Onset of photophobia, nystagmus, and hyperopia can occur in the first few years of life or later in childhood. Patients experience nephronophthisis, characterized by cystic kidney disease (medullary cystic kidney disease), reduced concentrating ability, and chronic tubulointerstitial nephritis, which progresses to end-stage renal disease. Hypertension is common.
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Ciliopathy sjogren larsson syndrome
Advances in Experimental Medicine and Biology, 2018Co-Authors: Alicia R P Aycinena, Stephen H. Tsang, Tarun SharmaAbstract:Glistening yellow-white crystalline inclusions in foveal and parafoveal areas are almost pathognomonic (Fig. 36.1). These inclusions are evident at 1-2 years old and increase with age. Patients may have corneal stromal opacities, punctate keratitis, myopia, and astigmatism. About 50% have pigmentary degeneration of the retina, with decreased visual acuity and marked photophobia. Patients have dry, scaly skin (ichthyosis). Affected infants tend to be born prematurely. They also have neurological problems due to leukoencephalopathy (affecting the white matter of the brain). Intellectual disability varies from mild to severe, along with dysarthria and delayed speech.
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Cellular imaging demonstrates genetic mosaicism in heterozygous carriers of an X-linked Ciliopathy gene.
European journal of human genetics : EJHG, 2013Co-Authors: Sung Pyo Park, In Hwan Hong, Stephen H. Tsang, Stanley ChangAbstract:Cellular imaging demonstrates genetic mosaicism in heterozygous carriers of an X-linked Ciliopathy gene
Karsten Boldt - One of the best experts on this subject based on the ideXlab platform.
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CFAP45 deficiency causes situs abnormalities and asthenospermia by disrupting an axonemal adenine nucleotide homeostasis module
Nature communications, 2020Co-Authors: Gerard W Dougherty, Karsten Boldt, Katsutoshi Mizuno, Tabea Nöthe-menchen, Yayoi Ikawa, Asaf Ta-shma, Isabella Aprea, Katsura Minegishi, Yuan Ping Pang, Petra PennekampAbstract:Axonemal dynein ATPases direct ciliary and flagellar beating via adenosine triphosphate (ATP) hydrolysis. The modulatory effect of adenosine monophosphate (AMP) and adenosine diphosphate (ADP) on flagellar beating is not fully understood. Here, we describe a deficiency of cilia and flagella associated protein 45 (CFAP45) in humans and mice that presents a motile Ciliopathy featuring situs inversus totalis and asthenospermia. CFAP45-deficient cilia and flagella show normal morphology and axonemal ultrastructure. Proteomic profiling links CFAP45 to an axonemal module including dynein ATPases and adenylate kinase as well as CFAP52, whose mutations cause a similar Ciliopathy. CFAP45 binds AMP in vitro, consistent with structural modelling that identifies an AMP-binding interface between CFAP45 and AK8. Microtubule sliding of dyskinetic sperm from Cfap45-/- mice is rescued with the addition of either AMP or ADP with ATP, compared to ATP alone. We propose that CFAP45 supports mammalian ciliary and flagellar beating via an adenine nucleotide homeostasis module.
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a high throughput genome wide sirna screen for ciliogenesis identifies new ciliary functional components and Ciliopathy genes
Cilia, 2015Co-Authors: Katarzyna Szymanska, Miriam Schmidts, Karsten Boldt, Dorus A Mans, Gabrielle Wheway, Dan Doherty, Zakia Abdelhamed, Thanhminh T Nguyen, G Todt, Kirsten A WunderlichAbstract:Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe the first whole genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource for investigation and interventions into the processes that are critical for the ciliary system. In total, we identified 83 candidate ciliogenesis and Ciliopathy genes, including 15 components of the ubiquitin-proteasome system. The validated hits also include 12 encoding G-protein-coupled receptors, and three encoding pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. Combining the screen with exome sequencing data identified recessive mutations in screen candidate genes as novel causes of ciliopathies, emphasizing the utility of our screen for Ciliopathy gene discovery. Our findings emphasize the relevance of global, unbiased functional and genetic screening approaches in understanding ciliogenesis complexity, and in identifying loss of function in unanticipated pathways of human genetic disease.
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differential requirements of ciliogenic Ciliopathy module components in restricting joubert syndrome associated arl13b to a c elegans inv like ciliary compartment
Cilia, 2012Co-Authors: Oliver E Blacque, Sebiha Cevik, Lara Clarke, Anna A W M Sanders, Karsten Boldt, Jeroen Van Reeuwijk, Marius Ueffing, Ronald Roepman, Erwin Van Wijk, H KremerAbstract:Cilium dysfunction causes disorders such as Meckel syndrome (MKS), Bardet-Biedl syndrome (BBS), Nephronophthisis (NPHP) and Joubert syndrome (JS). Most Ciliopathy proteins localize to cilia where they regulate developmental signaling and transport. Previously we showed that JS-associated Arl13b localises at proximal ciliary membranes, where it regulates transport in C. elegans. Now we employ C. elegans to investigate the molecular basis of Arl13b ciliary compartmentalisation. First we find that the localisation of C. elegans Arl13b (ARL-13) to proximal ciliary regions does not include transition zones. This localisation, reminiscent of the mammalian Inversin (Inv) ciliary compartment, requires an RVxP motif. Using quantitative imaging, Ciliopathy and ciliary transport genes were found to differentially restrict ARL-13 to cilia, with IFT, BBS and MKS gene mutants displaying varying ARL-13 accumulations explicitly at periciliary membranes. Specifically, we observed strong accumulations in IFT-B complex mutants, moderate accumulations in IFT-A, BBS and MKS mutants, and no accumulations in NPHP, septin or kinesin-2 mutants. Interestingly, within IFT/BBS/MKS mutant cilia, ARL-13 distributions were unaffected, as was ARL-13 ciliary mobility. Finally, using a TAP-tag immunoprecipitation approach from mammalian HEK293T cells and state-of-the-art mass spectrometry, we identified components of mammalian Arl13b-associated complexes, including the IFT-B subcomplex. These data show that ARL-13 localisation to an Inv-like ciliary compartment requires an RVxP motif and differential contributions by ciliary transport and Ciliopathy modules. Our data also suggest that IFT/BBS/MKS modules are not required for ARL-13 distribution and mobility within cilia, but rather its entry into cilia, perhaps by overcoming a transport barrier at the ciliary base.
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differential requirements of ciliogenic Ciliopathy module components in restricting joubert syndrome associated arl13b to a c elegans inv like ciliary compartment
Cilia, 2012Co-Authors: Oliver E Blacque, Sebiha Cevik, Lara Clarke, Anna A W M Sanders, Karsten Boldt, Jeroen Van Reeuwijk, Marius Ueffing, Ronald Roepman, Erwin Van Wijk, H KremerAbstract:Cilium dysfunction causes disorders such as Meckel syndrome (MKS), Bardet-Biedl syndrome (BBS), Nephronophthisis (NPHP) and Joubert syndrome (JS). Most Ciliopathy proteins localize to cilia where they regulate developmental signaling and transport. Previously we showed that JS-associated Arl13b localises at proximal ciliary membranes, where it regulates transport in C. elegans. Now we employ C. elegans to investigate the molecular basis of Arl13b ciliary compartmentalisation. First we find that the localisation of C. elegans Arl13b (ARL-13) to proximal ciliary regions does not include transition zones. This localisation, reminiscent of the mammalian Inversin (Inv) ciliary compartment, requires an RVxP motif. Using quantitative imaging, Ciliopathy and ciliary transport genes were found to differentially restrict ARL-13 to cilia, with IFT, BBS and MKS gene mutants displaying varying ARL-13 accumulations explicitly at periciliary membranes. Specifically, we observed strong accumulations in IFT-B complex mutants, moderate accumulations in IFT-A, BBS and MKS mutants, and no accumulations in NPHP, septin or kinesin-2 mutants. Interestingly, within IFT/BBS/MKS mutant cilia, ARL-13 distributions were unaffected, as was ARL-13 ciliary mobility. Finally, using a TAP-tag immunoprecipitation approach from mammalian HEK293T cells and state-of-the-art mass spectrometry, we identified components of mammalian Arl13b-associated complexes, including the IFT-B subcomplex. These data show that ARL-13 localisation to an Inv-like ciliary compartment requires an RVxP motif and differential contributions by ciliary transport and Ciliopathy modules. Our data also suggest that IFT/BBS/MKS modules are not required for ARL-13 distribution and mobility within cilia, but rather its entry into cilia, perhaps by overcoming a transport barrier at the ciliary base.
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the Ciliopathy associated protein homologs rpgrip1 and rpgrip1l are linked to cilium integrity through interaction with nek4 serine threonine kinase
Human Molecular Genetics, 2011Co-Authors: Karlien L M Coene, Karsten Boldt, Dorus A Mans, Johannes C Gloeckner, Jeroen Van Reeuwijk, Emine Bolat, Susanne Roosing, Stef J F LetteboerAbstract:Recent studies have established ciliary dysfunction as the underlying cause of a broad range of multi-organ phenotypes, known as 'ciliopathies'. Ciliopathy-associated proteins have a common site of action in the cilium, however, their overall importance for ciliary function differs, as implied by the extreme variability in Ciliopathy phenotypes. The aim of this study was to gain more insight in the function of two Ciliopathy-associated protein homologs, RPGR interacting protein 1 (RPGRIP1) and RPGRIP1-like protein (RPGRIP1L). Mutations in RPGRIP1 lead to the eye-restricted disease Leber congenital amaurosis, while mutations in RPGRIP1L are causative for Joubert and Meckel syndrome, which affect multiple organs and are at the severe end of the Ciliopathy spectrum. Using tandem affinity purification in combination with mass spectrometry, we identified Nek4 serine/threonine kinase as a prominent component of both the RPGRIP1- as well as the RPGRIP1L-associated protein complex. In ciliated cells, this kinase localized to basal bodies, while in ciliated organs, the kinase was predominantly detected at the ciliary rootlet. Down-regulation of NEK4 in ciliated cells led to a significant decrease in cilium assembly, pointing to a role for Nek4 in cilium dynamics. We now hypothesize that RPGRIP1 and RPGRIP1L function as cilium-specific scaffolds that recruit a Nek4 signaling network which regulates cilium stability. Our data are in line with previously established roles in the cilium of other members of the Nek protein family and define NEK4 as a Ciliopathy candidate gene.
H Kremer - One of the best experts on this subject based on the ideXlab platform.
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differential requirements of ciliogenic Ciliopathy module components in restricting joubert syndrome associated arl13b to a c elegans inv like ciliary compartment
Cilia, 2012Co-Authors: Oliver E Blacque, Sebiha Cevik, Lara Clarke, Anna A W M Sanders, Karsten Boldt, Jeroen Van Reeuwijk, Marius Ueffing, Ronald Roepman, Erwin Van Wijk, H KremerAbstract:Cilium dysfunction causes disorders such as Meckel syndrome (MKS), Bardet-Biedl syndrome (BBS), Nephronophthisis (NPHP) and Joubert syndrome (JS). Most Ciliopathy proteins localize to cilia where they regulate developmental signaling and transport. Previously we showed that JS-associated Arl13b localises at proximal ciliary membranes, where it regulates transport in C. elegans. Now we employ C. elegans to investigate the molecular basis of Arl13b ciliary compartmentalisation. First we find that the localisation of C. elegans Arl13b (ARL-13) to proximal ciliary regions does not include transition zones. This localisation, reminiscent of the mammalian Inversin (Inv) ciliary compartment, requires an RVxP motif. Using quantitative imaging, Ciliopathy and ciliary transport genes were found to differentially restrict ARL-13 to cilia, with IFT, BBS and MKS gene mutants displaying varying ARL-13 accumulations explicitly at periciliary membranes. Specifically, we observed strong accumulations in IFT-B complex mutants, moderate accumulations in IFT-A, BBS and MKS mutants, and no accumulations in NPHP, septin or kinesin-2 mutants. Interestingly, within IFT/BBS/MKS mutant cilia, ARL-13 distributions were unaffected, as was ARL-13 ciliary mobility. Finally, using a TAP-tag immunoprecipitation approach from mammalian HEK293T cells and state-of-the-art mass spectrometry, we identified components of mammalian Arl13b-associated complexes, including the IFT-B subcomplex. These data show that ARL-13 localisation to an Inv-like ciliary compartment requires an RVxP motif and differential contributions by ciliary transport and Ciliopathy modules. Our data also suggest that IFT/BBS/MKS modules are not required for ARL-13 distribution and mobility within cilia, but rather its entry into cilia, perhaps by overcoming a transport barrier at the ciliary base.
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differential requirements of ciliogenic Ciliopathy module components in restricting joubert syndrome associated arl13b to a c elegans inv like ciliary compartment
Cilia, 2012Co-Authors: Oliver E Blacque, Sebiha Cevik, Lara Clarke, Anna A W M Sanders, Karsten Boldt, Jeroen Van Reeuwijk, Marius Ueffing, Ronald Roepman, Erwin Van Wijk, H KremerAbstract:Cilium dysfunction causes disorders such as Meckel syndrome (MKS), Bardet-Biedl syndrome (BBS), Nephronophthisis (NPHP) and Joubert syndrome (JS). Most Ciliopathy proteins localize to cilia where they regulate developmental signaling and transport. Previously we showed that JS-associated Arl13b localises at proximal ciliary membranes, where it regulates transport in C. elegans. Now we employ C. elegans to investigate the molecular basis of Arl13b ciliary compartmentalisation. First we find that the localisation of C. elegans Arl13b (ARL-13) to proximal ciliary regions does not include transition zones. This localisation, reminiscent of the mammalian Inversin (Inv) ciliary compartment, requires an RVxP motif. Using quantitative imaging, Ciliopathy and ciliary transport genes were found to differentially restrict ARL-13 to cilia, with IFT, BBS and MKS gene mutants displaying varying ARL-13 accumulations explicitly at periciliary membranes. Specifically, we observed strong accumulations in IFT-B complex mutants, moderate accumulations in IFT-A, BBS and MKS mutants, and no accumulations in NPHP, septin or kinesin-2 mutants. Interestingly, within IFT/BBS/MKS mutant cilia, ARL-13 distributions were unaffected, as was ARL-13 ciliary mobility. Finally, using a TAP-tag immunoprecipitation approach from mammalian HEK293T cells and state-of-the-art mass spectrometry, we identified components of mammalian Arl13b-associated complexes, including the IFT-B subcomplex. These data show that ARL-13 localisation to an Inv-like ciliary compartment requires an RVxP motif and differential contributions by ciliary transport and Ciliopathy modules. Our data also suggest that IFT/BBS/MKS modules are not required for ARL-13 distribution and mobility within cilia, but rather its entry into cilia, perhaps by overcoming a transport barrier at the ciliary base.
Alicia R P Aycinena - One of the best experts on this subject based on the ideXlab platform.
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Ciliopathy: Alström Syndrome
Advances in experimental medicine and biology, 2018Co-Authors: Stephen H. Tsang, Alicia R P Aycinena, Tarun SharmaAbstract:Alstrom syndrome is an autosomal recessive disease with multisystem involvement, including cone-rod dystrophy, hearing loss, type 2 diabetes, insulin resistance with hyperinsulinemia, dilated cardiomyopathy, and progressive hepatic and renal failure. Patients present in childhood with photophobia and nystagmus, and mimic Leber congenital amaurosis (LCA). The fundus shows pigmentary retinopathy with peau d'orange appearance and some fine white dots like drusen around the macula; the disc is pale, with attenuated retinal vessels (Fig. 35.1). Patients have short stature; boys have hypogonadotropic hypogonadism and girls have polycystic ovary syndrome (PCOS). Obesity is always present, with markedly increased triglyceride and VLDL-C levels; arterial hypertension is diagnosed as early as 2 years of age. There is no polydactyly or syndactyly. About half have developmental delay, but intelligence is usually normal.
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Ciliopathy usher syndrome
Advances in Experimental Medicine and Biology, 2018Co-Authors: Alicia R P Aycinena, S Tsang, Tarun SharmaAbstract:Ciliopathies are a group of disorders caused by a defect in ciliogenesis, ciliary protein trafficking. Because nearly every cell in the body (including the photoreceptors) contains cilia, defects in ciliary proteins typically affect multiple organ systems. Usher syndrome is the most common syndromic cause of retinitis pigmentosa (RP) and accounts for 10–20% of cases of RP Inheritance is autosomal recessive, and the retinal dystrophy is usually rod-cone dystrophy (Figs. 32.1 and 32.2). These patients have RP with sensorineural hearing loss (partial or complete) since birth; some may have vestibular dysfunction. Most patients retain central vision of about 20/40 until about age 40. Usher Syndrome 1 (USH1): Profound congenital sensorineural hearing loss on audiometry, absent vestibular function, and typical RP (onset by 10 years of age); accounts for about 70% of all Usher cases. Patient may benefit from a cochlear implant. The retinitis pigmentosa occurs at an early age (childhood onset) and progress slowly. Usher Syndrome 2 (USH2): Moderate to severe congenital sensorineural hearing loss on audiometry (predominantly for higher frequencies), normal vestibular function, and typical RP (onset by 20 years of age); accounts for about 26% of all Usher cases. Usher Syndrome 3 (USH3): Progressive sensorineural hearing loss and typical RP (onset in second decade); accounts for about 4% of all Usher cases. Vestibular function is normal in about half of patients, but abnormal in the other half.
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Ciliopathy bardet biedl syndrome
Advances in Experimental Medicine and Biology, 2018Co-Authors: Alicia R P Aycinena, S Tsang, Tarun SharmaAbstract:Bardet-Biedl syndrome (BBS) is an autosomal recessive disease with a prevalence of about 1/125,000. The syndrome involves mixed rod-cone dystrophy (which becomes obvious by 6 years of age). About two thirds of patients have postaxial polydactyly, and sometimes syndactyly, brachydactyly, and/or clinodactyly may be present. Hypogonadism and renal involvement occur in about 40%, mental retardation in about 50%, and truncal obesity in about 70%; it is present early, along with insulin resistance, type 2 diabetes, dyslipidemia, and hypertension. Vision becomes markedly impaired by about age 30 years. The BBS is genetically heterogeneous entity with considerable phenotypic variability. Other associated problems include CNS-related ataxia, abnormal gait, and facial hypotonia, as well as anomalies such as high palate, hearing loss, and cardiac malformations. In males, there is oligospermia, leading to infertility. Around 50–80% of BBS patients have renal malformations (like cyst, agenesis or scarring) and renal dysfunction leading to end-stage renal disease. There are no pigmentary changes before the age of 1–2 years. Later, subtle pigmentary changes appear in the macula or peripapillary area. Several years later, pigments appear in the equatorial region, along with attenuation of retinal blood vessels and waxy pallor of the optic disc. Eventually, the macula may show atrophic changes (Figs. 33.1, 33.2 and 33.3). Electroretinography (ERG) shows involvement of rods and cones and is abnormal even before the fundus shows changes. A perimacular hyperfluorescent ring can be seen.
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Ciliopathy senior loken syndrome
Advances in Experimental Medicine and Biology, 2018Co-Authors: Alicia R P Aycinena, Stephen H. Tsang, Tarun SharmaAbstract:Senior-Loken syndrome is a rare autosomal recessive disease with a prevalence of 1:1,000,000. Retinopathy may progress as Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), or sector RP (Figs. 34.1 and 34.2). Onset of photophobia, nystagmus, and hyperopia can occur in the first few years of life or later in childhood. Patients experience nephronophthisis, characterized by cystic kidney disease (medullary cystic kidney disease), reduced concentrating ability, and chronic tubulointerstitial nephritis, which progresses to end-stage renal disease. Hypertension is common.
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Ciliopathy sjogren larsson syndrome
Advances in Experimental Medicine and Biology, 2018Co-Authors: Alicia R P Aycinena, Stephen H. Tsang, Tarun SharmaAbstract:Glistening yellow-white crystalline inclusions in foveal and parafoveal areas are almost pathognomonic (Fig. 36.1). These inclusions are evident at 1-2 years old and increase with age. Patients may have corneal stromal opacities, punctate keratitis, myopia, and astigmatism. About 50% have pigmentary degeneration of the retina, with decreased visual acuity and marked photophobia. Patients have dry, scaly skin (ichthyosis). Affected infants tend to be born prematurely. They also have neurological problems due to leukoencephalopathy (affecting the white matter of the brain). Intellectual disability varies from mild to severe, along with dysarthria and delayed speech.