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Approaches to Studying Polycystic Kidney Disease in Zebrafish
Published in Jinghua Hu, Yong Yu, Polycystic Kidney Disease, 2019
We can use immunostaining with antibodies against polarity markers to check the cell polarity and the whole-mount in situ hybridization or live imaging to check the nephron segment markers to detect convergent extension or cell migration. During zebrafish kidney development, the boundary of segment marker, for example, nbc1, shift in a proximal-direction overtime (e.g., from 1 to 3 dpf), and this shift is disrupted in all PKD models in zebrafish, including Ift88 and Inpp5e-depleted embryos (Figure 12.2d).31,33 Markers and transgenic lines are listed in Table 12.1.
Bardet−Biedl Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Differential diagnoses for BBS include conditions which demonstrate clinical resemblances, including McKusick-Kaufman syndrome (MKKS, autosomal recessive disorder; causing the triad of hydrometrocolpos, postaxial polydactyly, and congenital heart disease, as well as genitourinary abnormalities, underdeveloped lungs, gastrointestinal abnormalities, and kidney defects; due to mutations in the BBS6/MKKS gene), Alstrom syndrome (autosomal recessive disorder; causing cone-rod dystrophy, obesity, progressive sensorineural hearing impairment, dilated cardiomyopathy, insulin-resistant diabetes mellitus syndrome, and developmental delay; due to ALMS1 mutations), Joubert syndrome (autosomal recessive disorder; causing episodic hyperpnea, developmental delay, intellectual disability, hypotonia, oculomotor apraxia, ataxia, vermis hyoplasia or agenesis, characteristic molar tooth sign on cranial magnetic resonance imaging, retinal dystrophy, cystic dysplasia and nephronophthisis, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities; due to mutations in NPHP1, AHI1, CEP290/NPHP6, TMEM67/MKS3, RPGRIP1L, CC2D2A, ARL13B, INPP5E, OFD1, TMEM216, KIF7, TCTN1, TCTN2, TMEM237, CEP41, TMEM138, CPLANE1, and TTC21B), Senior−Løken syndrome (autosomal recessive disorder; causing retinitis pigmentosa, cystic renal dysplasia, nephronophthisis, medullary cystic kidneys, polycystic kidneys., cerebellar vermis hypoplasia, ataxia, developmental delay, intellectual disability, occipital encephalocele, and oculomotor apraxia; due to mutations in CEP290, NPHP1, NPHP3, NPHP4, IQCB1, and SDCCAG8), Meckel syndrome (autosomal recessive disorder causing the triad of occipital encephalocele, large polycystic kidneys, and postaxial polydactyly as well as orofacial clefting, genital anomalies, CNS malformations, fibrosis of the liver, pulmonary hypoplasia; due to distinct mutations in the BBS2, BBS4, and BBS6 genes), Leber congenital amaurosis (causing severe dystrophy of the retina, nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia, and keratoconus, eye poking, pressing, and rubbing; due to mutations n GUCY2D, RPE65, SPATA7, AIPL1, LCA5, RPGRIP1, CRX, CRB1, IMPDH1, RD3, RDH12, and CEP290; mutations in LRAT and TULP1 may be associated with an LCA-like phenotype), Biemon syndrome type II (autosomal recessive disorder; causing iris coloboma, intellectual disability, obesity, polydactyly, hypogonadism, hydrocephalus, and facial dysostosis), Prader−Willi syndrome (genetic disorder; causing hypotonia, feeding difficulties, failure to thrive, short stature, genital abnormalities, excessive appetite, progressive obesity, cognitive impairment, temper tantrums, obsessive/compulsive behavior, skin picking; due to nonfunctional genes in a region of chromosome 15) [26,37].
Challenges and resources in adult life with Joubert syndrome: issues from an international classification of functioning (ICF) perspective
Published in Disability and Rehabilitation, 2022
Romina Romaniello, Chiara Gagliardi, Patrizia Desalvo, Livio Provenzi, Roberta Battini, Enrico Bertini, Maria Teresa Bonati, Marilena Briguglio, Stefano D’Arrigo, Maria Teresa Dotti, Lucio Giordano, Claudio Macaluso, Isabella Moroni, Sara Nuovo, Margherita Santucci, Sabrina Signorini, Franco Stanzial, Enza Maria Valente, Renato Borgatti
Consistent with the CNS involvement in JS and with the frequent occurrence of retinal and hepatic disease, severe impairments in body functions and structures emerged in relation to the nervous system as well as with vision and auditory systems [5]. Interestingly, no other body functions and structures were reported as severely affected, whereas mild deficits were reported both for global and specific mental functions, including emotional regulation, perception and high-order cognitive tasks. These findings confirm and further expand previous evidence on children with JS [6,11], which highlighted a phenotypic complexity related to the interplay of visual, motor and cognitive defects. Notably, although the present study confirms the relative high prevalence of retinal and hepatic problems, kidneys involvement was reported in two patients (5.6%), a frequency which is lower than expected according to former studies from us and others, reporting renal complications in up to 25–30% of JS patients [1,19,20]. On the one hand, as suggested by Dempsey and colleagues [16], this discrepancy may depend on the fact that patients with more severe kidney diseases are less likely to survive to adult age. Indeed, in our sample, two patients that did not survive to the follow-up died due to rental complications. On the other hand, mild renal involvement may remain clinically asymptomatic. Consistently, in the present study, many adult JS patients carried mutations in genes that are known to spare kidneys or to present only a minimal risk of renal disease (e.g., AHI1, INPP5E, CPLANE1).
Severe retinitis pigmentosa with posterior staphyloma in a family with c.886C>A p.(Lys296Glu) RHO mutation
Published in Ophthalmic Genetics, 2019
Vasily M. Smirnov, Caroline Marks, Isabelle Drumare, Sabine Defoort-Dhellemmes, Claire-Marie Dhaenens
Association between some specific mutations in IRD genes and posterior pole staphyloma were previously reported. Indeed, retinal ciliopathies, either isolated (C21Orf2-related retinitis pigmentosa (3)) or syndromic (INPP5E and AHI1-related Joubert syndrome (10)) can frequently lead to staphyloma formation. Posterior staphyloma may also be an integral part of clinical picture of IRD, for instance in MRCS-syndrome (7), which could be BEST1-linked or not (11). None of our patients had an early cataract or microcornea. Mutations in other IRD-associated genes, as EYS (12), or RDH12 (13), are anecdotally reported in cases of RP with PPS.
Clinical characteristics of high myopia in female carriers of pathogenic RPGR mutations: a case series and review of the literature
Published in Ophthalmic Genetics, 2023
Matthew Tran, Masha Kolesnikova, Angela H. Kim, Tia Kowal, Ke Ning, Vinit B. Mahajan, Stephen H. Tsang, Yang Sun
In contrast to this trend, other authors have described pedigrees with mutations in exons 1–14 of RPGR, such as in patient 3, that are also correlated with phenotypic high myopia in female carriers (8,35,36). Particularly, Banin et al. reported a missense substitution (c.g823a, p.Gly275Ser) within exon 8 in an Israeli family, where obligate carriers suffered from high myopia, low visual acuity, restricted visual fields, and reduced ERG amplitudes (36). However, this identical variant was also identified in two Danish families, where obligate carriers had no visual complaints and normal to slightly diminished retinal function (37). Because the disease-related RPGR haplotypes in the aforementioned families were different, Banin suggested that additional genes linked to RPGR may explain the high phenotypic variability resulting from RPGR mutations and be related to the myopia observed in affected carriers (36). Exons 1–10 of RPGR encode a domain homologous to the Regulator of Chromosome Condensation 1 (RCC1), a guanine nucleotide exchange factor for Ran, consisting of seven blade-shaped beta sheets forming a beta-propeller structure (Figure 6) (12). Binding sites for proteins such as RPGR interacting protein 1 (RPGRIP1) and the delta subunit of rod cyclic GMP phosphodiesterase (PDE6δ) exist in the RCC1-like domain. The deletion (c.1100delC, p.Pro367Leufs *14) in patient 3 occurred in exon 10 of RPGR, indicating a potential role of N-terminal protein interactions in the pathogenesis of disease. Inositol polyphosphate-5-phosphatase 5E (INPP5E), a potential ciliary cargo protein that interacts with the N-terminus of RPGR, has been recently implicated in the pathogenesis of RPGR-associated ciliopathies and non-syndromic inherited retinal degenerations (38,39).