An Update on the Genetics of Usher Syndrome
José M. Millán,Elena Aller,Teresa Jaijo,Fiona Blanco-Kelly,Ascension Gimenez-Pardo,Carmen Ayuso +5 more
TLDR
Usher syndrome is an autosomal recessive disease characterized by hearing loss, retinitis pigmentosa (RP), and, in some cases, vestibular dysfunction, and is the most common cause underlying deafness and blindness of genetic origin.Abstract:
Usher syndrome (USH) is an autosomal recessive disease characterized by hearing loss, retinitis pigmentosa (RP), and, in some cases, vestibular dysfunction. It is clinically and genetically heterogeneous and is the most common cause underlying deafness and blindness of genetic origin. Clinically, USH is divided into three types. Usher type I (USH1) is the most severe form and is characterized by severe to profound congenital deafness, vestibular areflexia, and prepubertal onset of progressive RP. Type II (USH2) displays moderate to severe hearing loss, absence of vestibular dysfunction, and later onset of retinal degeneration. Type III (USH3) shows progressive postlingual hearing loss, variable onset of RP, and variable vestibular response. To date, five USH1 genes have been identified: MYO7A (USH1B), CDH23 (USH1D), PCDH15 (USH1F), USH1C(USH1C), and USH1G(USH1G). Three genes are involved in USH2, namely, USH2A (USH2A), GPR98 (USH2C), and DFNB31 (USH2D). USH3 is rare except in certain populations, and the gene responsible for this type is USH3A.read more
Citations
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Journal ArticleDOI
Retinitis Pigmentosa: Genes and Disease Mechanisms
Francesco Parmeggiani,Francesco Sorrentino,Diego Ponzin,Vanessa Barbaro,Stefano Ferrari,Enzo Di Iorio +5 more
TL;DR: Which genes are involved in the genesis of RP and how mutations can lead to retinal degeneration are reviewed to reveal important information with respect to the likelihood of disease development and choices of therapy.
Journal ArticleDOI
Cadherins and neuropsychiatric disorders.
TL;DR: Genes encoding members of the cadherin superfamily are of special interest in the pathogenesis of neuropsychiatric disease because cadherins play a pivotal role in the development of the neural circuitry as well as in mature synaptic function.
Journal ArticleDOI
Effective delivery of large genes to the retina by dual AAV vectors
Ivana Trapani,Pasqualina Colella,Andrea Sommella,Carolina Iodice,Giulia Cesi,Sonia de Simone,Elena Marrocco,Settimio Rossi,Massimo Giunti,Arpad Palfi,Gwyneth Jane Farrar,Roman S. Polishchuk,Alberto Auricchio +12 more
TL;DR: It is found that dual trans‐splicing and hybrid vectors transduce efficiently mouse and pig photoreceptors to levels that, albeit lower than those achieved with a single AAV, resulted in significant improvement of the retinal phenotype of mouse models of STGD and USH1B.
Journal ArticleDOI
Understanding photoreceptor outer segment phagocytosis: use and utility of RPE cells in culture.
TL;DR: Comparisons and differences of primary, immortalized, and stem cell-derived RPE cells in culture to R PE cells in situ with respect to phagocytic function are compared.
Journal ArticleDOI
Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study
Polona Le Quesne Stabej,Zubin Saihan,Nell Rangesh,Heather B Steele-Stallard,John C. Ambrose,Alison J. Coffey,Jenny Emmerson,Elene Haralambous,Yasmin Hughes,Karen P. Steel,Linda M. Luxon,Andrew R. Webster,Maria Bitner-Glindzicz,Maria Bitner-Glindzicz +13 more
TL;DR: It is concluded that digenic inheritance does not make a significant contribution to Usher syndrome; the observation of multiple variants in different genes is likely to reflect polymorphic variation, rather than digenic effects.
References
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Journal ArticleDOI
Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells.
Piotr Kazmierczak,Hirofumi Sakaguchi,Joshua Tokita,Elizabeth M. Wilson-Kubalek,Ronald A. Milligan,Ulrich Müller,Bechara Kachar +6 more
TL;DR: The studies define the molecular composition of tip links and provide a conceptual base for exploring the mechanisms of sensory impairment associated with mutations in CDH23 and PCDH15.
Journal ArticleDOI
Usher Syndrome 1D and Nonsyndromic Autosomal Recessive Deafness DFNB12 Are Caused by Allelic Mutations of the Novel Cadherin-Like Gene CDH23
Julie M. Bork,Linda M. Peters,Saima Riazuddin,Saima Riazuddin,S. L. Bernstein,Zubair M. Ahmed,Zubair M. Ahmed,Seth L. Ness,Robert C. Polomeno,Arabandi Ramesh,Arabandi Ramesh,Melvin D. Schloss,C. R. Srikumari Srisailpathy,C. R. Srikumari Srisailpathy,Sigrid Wayne,Susan Bellman,Dilip Desmukh,Zahoor Ahmed,Shaheen N. Khan,Vazken M. Der Kaloustian,X. Cindy Li,Anil K. Lalwani,Sheikh Riazuddin,Maria Bitner-Glindzicz,Walter E. Nance,Xue-Zhong Liu,Graeme Wistow,Richard J.H. Smith,Andrew J. Griffith,Edward R. Wilcox,Thomas B. Friedman,Robert J. Morell +31 more
TL;DR: Genes causing nonsyndromic autosomal recessive deafness (DFNB12) and deafness associated with retinitis pigmentosa and vestibular dysfunction (USH1D) were previously mapped to overlapping regions of chromosome 10q21-q22, but mutations in a novel cadherin-like gene, CDH23, were found both in families with DFNB12 and in Families with USH1D.
Journal ArticleDOI
Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D
Hanno J. Bolz,von Brederlow B,Alfredo Ramirez,Elizabeth C. Bryda,Kerstin Kutsche,Hans Gerd Nothwang,Mathias W. Seeliger,del C-Salcedó Cabrera M,Vila Mc,Molina Op,Andreas Gal,Christian Kubisch +11 more
TL;DR: The data show that different mutations in CDH23 result in USH1D with a variable retinal phenotype, and it is shown that mutations in the mouse ortholog cause disorganization of inner ear stereocilia and deafness in the waltzer mouse.
Journal ArticleDOI
Prevalence of permanent childhood hearing impairment in the United Kingdom and implications for universal neonatal hearing screening: questionnaire based ascertainment study.
TL;DR: Prevalence of confirmed permanent childhood hearing impairment increases until the age of 9 years to a level higher than previously estimated, relative to current yields of universal neonatal hearing screening in the United Kingdom.
Journal ArticleDOI
A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C.
Elisabeth Verpy,Michel Leibovici,Ingrid Zwaenepoel,Xue Zhong Liu,Andreas Gal,Nabiha Salem,Ahmad M. Mansour,Stéphane Blanchard,Ichiro Kobayashi,Bronya J.B. Keats,Rima Slim,Christine Petit +11 more
TL;DR: A gene underlying USH1C is identified, encoding a PDZ-domain–containing protein, harmonin, in a subtracted mouse cDNA library derived from inner ear sensory areas, and it is proposed that Ush1C also underlies the DFNB18 form of isolated deafness.
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