scholarly journals An Update on the Genetics of Usher Syndrome

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
José M. Millán ◽  
Elena Aller ◽  
Teresa Jaijo ◽  
Fiona Blanco-Kelly ◽  
Ascensión Gimenez-Pardo ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Usher Syndrome ◽  
Severe Form ◽  
Vestibular Dysfunction ◽  
Type I ◽  
Type Ii ◽  
Genetic Origin ◽  
Vestibular Response

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), andUSH1G(USH1G). Three genes are involved in USH2, namely,USH2A(USH2A),GPR98(USH2C), andDFNB31(USH2D). USH3 is rare except in certain populations, and the gene responsible for this type isUSH3A.

scholarly journals Novel USH1G homozygous variant underlying USH2-like phenotype of Usher syndrome

2019 ◽  
pp. 112067211987939
Author(s):  
Fabiana D’Esposito ◽  
Viviana Randazzo ◽  
Gilda Cennamo ◽  
Nicola Centore ◽  
Paolo Enrico Maltese ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Retinitis Pigmentosa ◽  
Sensorineural Hearing Loss ◽  
Hearing Impairment ◽  
Usher Syndrome ◽  
Age At Onset ◽  
Vestibular Dysfunction ◽  
Sensorineural Hearing ◽  
Type I ◽  
Missense Variation

Purpose: Usher syndrome (USH) is an autosomal recessive disorder characterized by congenital sensorineural hearing impairment and retinitis pigmentosa. Classification distinguishes three clinical types of which type I (USH1) is the most severe, with vestibular dysfunction as an added feature. To date, 15 genes and 3 loci have been identified with the USH1G gene being an uncommon cause of USH. We describe an atypical USH1G-related phenotype caused by a novel homozygous missense variation in a patient with profound hearing impairment and relatively mild retinitis pigmentosa, but no vestibular dysfunction. Methods: A 26-year-old female patient with profound congenital sensorineural hearing loss, nyctalopia and retinitis pigmentosa was studied. Audiometric, vestibular and ophthalmologic examination was performed. A panel of 13 genes was tested by next-generation sequencing (NGS). Results: While the hearing loss was confirmed to be profound, the vestibular function resulted normal. Although typical retinitis pigmentosa was present, the age at onset was unusually late for USH1 syndrome. A novel homozygous missense variation (c.1187T>A, p.Leu396Gln) in the USH1G gene has been identified as causing the disease in our patient. Conclusions: Genetic and phenotypic heterogeneity are very common in both isolated and syndromic retinal dystrophies and sensorineural hearing loss. Our findings widen the spectrum of USH allelic disorders and strength the concept that variants in genes that are classically known as underlying one specific clinical USH subtype might result in unexpected phenotypes.

scholarly journals The Study of a 231 French Patient Cohort Significantly Extends the Mutational Spectrum of the Two Major Usher Genes MYO7A and USH2A

2021 ◽  
Vol 22 (24) ◽  
pp. 13294
Author(s):  
Luke Mansard ◽  
David Baux ◽  
Christel Vaché ◽  
Catherine Blanchet ◽  
Isabelle Meunier ◽  
...  
Keyword(s):  
Massively Parallel Sequencing ◽  
Splice Variants ◽  
Usher Syndrome ◽  
Genetic Diagnosis ◽  
Autosomal Recessive Disorder ◽  
Severe Form ◽  
High Rate ◽  
Type I ◽  
Type Ii ◽  
Causal Genes

Usher syndrome is an autosomal recessive disorder characterized by congenital hearing loss combined with retinitis pigmentosa, and in some cases, vestibular areflexia. Three clinical subtypes are distinguished, and MYO7A and USH2A represent the two major causal genes involved in Usher type I, the most severe form, and type II, the most frequent form, respectively. Massively parallel sequencing was performed on a cohort of patients in the context of a molecular diagnosis to confirm clinical suspicion of Usher syndrome. We report here 231 pathogenic MYO7A and USH2A genotypes identified in 73 Usher type I and 158 Usher type II patients. Furthermore, we present the ACMG classification of the variants, which comprise all types. Among them, 68 have not been previously reported in the literature, including 12 missense and 16 splice variants. We also report a new deep intronic variant in USH2A. Despite the important number of molecular studies published on these two genes, we show that during the course of routine genetic diagnosis, undescribed variants continue to be identified at a high rate. This is particularly pertinent in the current era, where therapeutic strategies based on DNA or RNA technologies are being developed.

scholarly journals Classical Xanthinuria in Nine Israeli Families and Two Isolated Cases from Germany: Molecular, Biochemical and Population Genetics Aspects

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 788
Author(s):  
Hava Peretz ◽  
Ayala Lagziel ◽  
Florian Bittner ◽  
Mustafa Kabha ◽  
Meirav Shtauber-Naamati ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Heterologous Protein ◽  
Heterologous Protein Expression ◽  
Type I ◽  
Type Ii ◽  
Amino Acid Residues ◽  
Cysteine Desulfurase ◽  
Cofactor Binding ◽  
Pathogenic Variants ◽  
Expression Studies

Classical xanthinuria is a rare autosomal recessive metabolic disorder caused by variants in the XDH (type I) or MOCOS (type II) genes. Thirteen Israeli kindred (five Jewish and eight Arab) and two isolated cases from Germany were studied between the years 1997 and 2013. Four and a branch of a fifth of these families were previously described. Here, we reported the demographic, clinical, molecular and biochemical characterizations of the remaining cases. Seven out of 20 affected individuals (35%) presented with xanthinuria-related symptoms of varied severity. Among the 10 distinct variants identified, six were novel: c.449G>T (p.(Cys150Phe)), c.1434G>A (p.(Trp478*)), c.1871C>G (p.(Ser624*)) and c.913del (p.(Leu305fs*1)) in the XDH gene and c.1046C>T (p.(Thr349Ileu)) and c.1771C>T (p.(Pro591Ser)) in the MOCOS gene. Heterologous protein expression studies revealed that the p.Cys150Phe variant within the Fe/S-I cluster-binding site impairs XDH biogenesis, the p.Thr349Ileu variant in the NifS-like domain of MOCOS affects protein stability and cysteine desulfurase activity, while the p.Pro591Ser and a previously described p.Arg776Cys variant in the C-terminal domain affect Molybdenum cofactor binding. Based on the results of haplotype analyses and historical genealogy findings, the potential dispersion of the identified variants is discussed. As far as we are aware, this is the largest cohort of xanthinuria cases described so far, substantially expanding the repertoire of pathogenic variants, characterizing structurally and functionally essential amino acid residues in the XDH and MOCOS proteins and addressing the population genetic aspects of classical xanthinuria.

Magnetic resonance imaging findings of adult-onset glutaric aciduria type I

2007 ◽  
Vol 48 (5) ◽  
pp. 557-559 ◽  
Author(s):  
G. Sonmez ◽  
H. Mutlu ◽  
E. Ozturk ◽  
H. O. Sildiroglu ◽  
A. T. Keskin ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Glutaric Aciduria Type ◽  
Type I ◽  
Imaging Findings ◽  
Resonance Imaging ◽  
Glutaric Aciduria ◽  
Glutaric Acidemia Type I ◽  
Glutaric Aciduria Type I

Glutaric aciduria or glutaric acidemia type I, an autosomal recessive disease, usually presents with an acute encephalopathic crisis in young children. We report the magnetic resonance (MR) and proton MR spectroscopy (MRS) imaging findings of a previously healthy 20-year-old man who presented with recurrent headaches. Organic acids from the patient's urine contained large amounts of adipate, glutarate, and 3-hydroxyglutarate consistent with glutaric aciduria type I.

scholarly journals Intracranial Calcifications in Autoimmune Polyendocrine Ectodermal Dystrophy Syndrome (APECED): About A Case Report

2021 ◽  
pp. 1-3
Author(s):  
Benfaddoul O ◽  
◽  
Zouita B ◽  
El azzouzi B ◽  
Basraoui N ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Chronic Mucocutaneous Candidiasis ◽  
Type I ◽  
Syndrome Type ◽  
Autoimmune Polyglandular Syndrome ◽  
Mucocutaneous Candidiasis ◽  
Autoimmune Polyendocrinopathy ◽  
Life Threatening ◽  
Autoimmune Polyglandular Syndrome Type

Autoimmune polyendocrinopathy ectodermal dystrophy (APECED), also known as autoimmune polyglandular syndrome type I (APS I), is an uncommon, but debilitating autosomal recessive disease caused by mutations in the autoimmune regulator (AIRE), It is characterized by a broad and diverse clinical spectrum which can lead to severe metabolic alterations and eventually life-threatening events. Hypoparathyroidism is one of the major criteria for clinical diagnosis, in addition to chronic mucocutaneous candidiasis and autoimmune adrenal insufficiency. This component is responsible for the forming of brain calcifications which tend to have a characteristic predilection for the basal ganglia. In this article, we report an additional case to the literature and provide a literature review of the expanding radiological spectrum of this syndrome

Congenital Erythropoietic Porphyria: Prenatal Diagnosis and Autopsy Findings in Two Sibling Fetuses

2001 ◽  
Vol 4 (2) ◽  
pp. 180-184 ◽  
Author(s):  
F. Daïkha-Dahmane ◽  
M. Dommergues ◽  
F. Narcy ◽  
M.C. Gubler ◽  
Y. Dumez ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Amniotic Fluid ◽  
Histological Examination ◽  
Autosomal Recessive ◽  
Dna Analysis ◽  
Autosomal Recessive Disease ◽  
Type I ◽  
Autopsy Findings ◽  
Congenital Erythropoietic Porphyria ◽  
Made In

Congenital erythropoietic porphyria is an autosomal recessive disease characterized by a deficiency of uroporphyrinogen III cosynthetase activity, with diffuse tissue accumulation of specific type I porphyrins. The diagnosis of this disease was made in two fetuses, who were siblings, and from a Caucasian nonconsanguinous family. The first fetus died in utero with hydrops fetalis and anemia, but without an etiopathogenic diagnosis. In the second case, the diagnosis was based on pink fluorescence of the amniotic fluid examined fortuitously in sunlight. DNA analysis showed that the fetus was heteroallelic for the mutation C73R. The autopsy showed brown skin, and at histological examination, porphyrin pigment was deposited in many tissues. Retrospectively, similar deposits were found in the tissues of the first fetus.

USH2A variants in Chinese patients with Usher syndrome type II and non-syndromic retinitis pigmentosa

2020 ◽  
pp. bjophthalmol-2019-315786 ◽  
Author(s):  
Tian Zhu ◽  
De-Fu Chen ◽  
Lei Wang ◽  
Shijing Wu ◽  
Xing Wei ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Retinitis Pigmentosa ◽  
Usher Syndrome ◽  
Chinese Patients ◽  
Syndrome Type ◽  
Type Ii ◽  
Phenotype Correlation ◽  
Clinical Visit ◽  
Younger Age ◽  
Usher Syndrome Type

AimsTo reveal the Usher syndrome type IIA (USH2A) gene variant profile in a large cohort of Chinese patients with non-syndromic retinitis pigmentosa (RP) or Usher syndrome type II (USH2) and to explore the genotype–phenotype correlation.MethodsTargeted exome capture plus next-generation sequencing confirmed that 284 patients from 260 unrelated Chinese families carried USH2A disease-associated variants. Both personal medical history and family histories were reviewed. Ocular examinations were performed and audiograms were recorded if hearing loss was suspected. The genotype–phenotype correlation was evaluated by statistical analyses.ResultsA total of 230 variants in the USH2A gene were identified, of which 90 (39.13%) were novel. The most common variants in the RP and USH2 probands were p.Cys934Trp and p.Tyr2854_2894del, respectively, and 26.42% and 63.64% of the alleles in the RP and USH2 groups were truncating, respectively. Patients harbouring biallelic truncating variants had a younger age at the initial clinical visit and symptom onset than patients with missense variants; furthermore, the patients with USH2 had a younger age at the initial clinical visit and nyctalopia onset compared with the patients with RP (p<0.001). For the patients with USH2, the age of nyctalopia onset was positively correlated with that of hearing loss (p<0.05, r=0.219). In addition, three pseudo-dominant pedigrees were identified carrying biallelic USH2A variants.ConclusionsThis study enrolled the largest cohort of Chinese patients with USH2A and identified the most prevalent USH2A variants in USH2 and RP. We found that the patients with USH2 had more truncating variants and experienced an earlier decline in visual function. The findings enhance the current knowledge of USH2A heterogeneity and provide valuable information for future therapies.

scholarly journals Outcomes of Late Implantation in Usher Syndrome Patients

2016 ◽  
Vol 21 (02) ◽  
pp. 140-143 ◽  
Author(s):  
Ana Hoshino ◽  
Agustina Echegoyen ◽  
Maria Goffi-Gomez ◽  
Robinson Tsuji ◽  
Ricardo Bento
Keyword(s):  
Hearing Loss ◽  
Retrospective Study ◽  
Speech Perception ◽  
Cochlear Implants ◽  
Pure Tone ◽  
Autosomal Recessive ◽  
Usher Syndrome ◽  
Autosomal Recessive Disorder ◽  
Auditory Pathways ◽  
One Year

Introduction Usher syndrome (US) is an autosomal recessive disorder characterized by hearing loss and progressive visual impairment. Some deaf Usher syndrome patients learn to communicate using sign language. During adolescence, as they start losing vision, they are usually referred to cochlear implantation as a salvage for their new condition. Is a late implantation beneficial to these children? Objective The objective of this study is to describe the outcomes of US patients who received cochlear implants at a later age. Methods This is a retrospective study of ten patients diagnosed with US1. We collected pure-tone thresholds and speech perception tests from pre and one-year post implant. Results Average age at implantation was 18.9 years (5–49). Aided average thresholds were 103 dB HL and 35 dB HL pre and one-year post implant, respectively. Speech perception was only possible to be measured in four patients preoperatively, who scored 13.3; 26.67; 46% vowels and 56% 4-choice. All patients except one had some kind of communication. Two were bilingual. After one year of using the device, seven patients were able to perform the speech tests (from four-choice to close set sentences) and three patients abandoned the use of the implant. Conclusion We observed that detection of sounds can be achieved with late implantation, but speech recognition is only possible in patients with previous hearing stimulation, since it depends on the development of hearing skills and the maturation of the auditory pathways.

scholarly journals Usher syndrome Type I in an adult Nepalese male: a rare case report

2018 ◽  
Vol 9 (2) ◽  
pp. 203-205
Author(s):  
Sabin Sahu ◽  
Sanjay Kumar Singh
Keyword(s):  
Hearing Loss ◽  
Retinitis Pigmentosa ◽  
Genetic Disorder ◽  
Usher Syndrome ◽  
Type I ◽  
Syndrome Type ◽  
Profound Hearing Loss ◽  
Rare Case Report ◽  
Different Populations ◽  
Usher Syndrome Type

Usher syndrome, also known as retinitis pigmentosa-dysacusis syndrome, is an extremely rare genetic disorder, characterized by retinitis pigmentosa (RP) and congenital sensorineural hearing loss. It has been estimated to account for 3-6% of the congenitally deaf population, upto 8-33% of individuals with RP and half of all cases with combined deafness and blindness (Vernon M,1969; Boughman JA et al,1983). The prevalence of Usher syndrome have been reported to range from 3.5 to 6.2 per 100,000 in different populations (Vernon M,1969; Boughman JA et al,1983; Yan D et al, 2010).We report a case of Usher syndrome type I in an adult Nepalese male with typical congenital profound hearing loss, and night blindness secondary to retinitis pigmentosa.

scholarly journals Usher Syndrome: Genetics of a Human Ciliopathy

2021 ◽  
Vol 22 (13) ◽  
pp. 6723
Author(s):  
Carla Fuster-García ◽  
Belén García-Bohórquez ◽  
Ana Rodríguez-Muñoz ◽  
Elena Aller ◽  
Teresa Jaijo ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Retinitis Pigmentosa ◽  
Sensorineural Hearing Loss ◽  
Autosomal Recessive ◽  
Age Of Onset ◽  
Usher Syndrome ◽  
Organ Of Corti ◽  
Sensorineural Hearing ◽  
Protein Network ◽  
Phenotype Correlation

Usher syndrome (USH) is an autosomal recessive syndromic ciliopathy characterized by sensorineural hearing loss, retinitis pigmentosa and, sometimes, vestibular dysfunction. There are three clinical types depending on the severity and age of onset of the symptoms; in addition, ten genes are reported to be causative of USH, and six more related to the disease. These genes encode proteins of a diverse nature, which interact and form a dynamic protein network called the “Usher interactome”. In the organ of Corti, the USH proteins are essential for the correct development and maintenance of the structure and cohesion of the stereocilia. In the retina, the USH protein network is principally located in the periciliary region of the photoreceptors, and plays an important role in the maintenance of the periciliary structure and the trafficking of molecules between the inner and the outer segments of photoreceptors. Even though some genes are clearly involved in the syndrome, others are controversial. Moreover, expression of some USH genes has been detected in other tissues, which could explain their involvement in additional mild comorbidities. In this paper, we review the genetics of Usher syndrome and the spectrum of mutations in USH genes. The aim is to identify possible mutation associations with the disease and provide an updated genotype–phenotype correlation.

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