New clinical and molecular evidence linking mutations in
            <i>ARSG</i>
            to Usher syndrome type IV

Peter, Virginie G.; Quinodoz, Mathieu; Sadio, Silvia; Held, Sebastian; Rodrigues, Márcia; Soares, Marta; Sousa, Ana Berta; Coutinho-Santos, Luísa; Damme, Markus; Rivolta, Carlo

doi:10.1002/humu.24150

Cited by 33 publications

(28 citation statements)

References 37 publications

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“…Consequently, CEP250 is now categorized as an USH-like gene. Recently, three studies with comparable cases identified ARSG mutations in atypical USH patients, designated as USH type 4 [128][129][130]. This appears to be a robust new candidate gene responsible for the disease, and ARSG should be included in upcoming genetic screenings.…”

Section: Other Related Genesmentioning

confidence: 99%

Usher Syndrome: Genetics of a Human Ciliopathy

Fuster-García

García‐Bohórquez

Rodríguez-Muñoz

et al. 2021

IJMS

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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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Section: Other Related Genesmentioning

confidence: 99%

Usher Syndrome: Genetics of a Human Ciliopathy

Fuster-García

García‐Bohórquez

Rodríguez-Muñoz

et al. 2021

IJMS

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“…Specifically, SGSH removes the sulfate group from N-Sulfoglucosamine by hydrolysis to produce D-Glucosamine [15]; when SGSH activity is absent, subsequent steps in the HS degradation pathway (e.g., NAGLU-mediated acetylglucosaminidase activity impaired in MPS IIIB, HGSNAT-mediated acetyltransferase activity which is impaired in MPS IIIC, or GNS-mediated sulfatase activity in MPS IIID) cannot occur. Another subtype, putatively referred to as MPS IIIE, is thought to result from arylsulfatase G (ARSG) dysfunction, but this has only been observed in animal models [16,17] and has yet to be described in a human patient (most ARSG mutations are instead associated with Usher syndrome type 4 [OMIM 6181440]) [18][19][20][21]. MPS IIIA, the most common of the MPS III subtypes [22], tends to exhibit greater clinical severity and progresses more rapidly than other MPS III subtypes [10].…”

Section: Introductionmentioning

confidence: 99%

An Engineered sgsh Mutant Zebrafish Recapitulates Molecular and Behavioural Pathobiology of Sanfilippo Syndrome A/MPS IIIA

Douek

Khabooshan

Henry

et al. 2021

IJMS

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Mucopolysaccharidosis IIIA (MPS IIIA, Sanfilippo syndrome type A), a paediatric neurological lysosomal storage disease, is caused by impaired function of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH) resulting in impaired catabolism of heparan sulfate glycosaminoglycan (HS GAG) and its accumulation in tissues. MPS IIIA represents a significant proportion of childhood dementias. This condition generally leads to patient death in the teenage years, yet no effective therapy exists for MPS IIIA and a complete understanding of the mechanisms of MPS IIIA pathogenesis is lacking. Here, we employ targeted CRISPR/Cas9 mutagenesis to generate a model of MPS IIIA in the zebrafish, a model organism with strong genetic tractability and amenity for high-throughput screening. The sgshΔex5−6 zebrafish mutant exhibits a complete absence of Sgsh enzymatic activity, leading to progressive accumulation of HS degradation products with age. sgshΔex5−6 zebrafish faithfully recapitulate diverse CNS-specific features of MPS IIIA, including neuronal lysosomal overabundance, complex behavioural phenotypes, and profound, lifelong neuroinflammation. We further demonstrate that neuroinflammation in sgshΔex5−6 zebrafish is largely dependent on interleukin-1β and can be attenuated via the pharmacological inhibition of Caspase-1, which partially rescues behavioural abnormalities in sgshΔex5−6 mutant larvae in a context-dependent manner. We expect the sgshΔex5−6 zebrafish mutant to be a valuable resource in gaining a better understanding of MPS IIIA pathobiology towards the development of timely and effective therapeutic interventions.

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“…In 2018, Khateb et al reported mutations in this gene in a family with “atypical” Usher [ 111 ]. Subsequently, it has been described as Usher 4, but this new entity has not been widely reported and accepted to date [ 111 , 112 , 113 , 114 ]. The introduction of a new clinical type USH4 is not widely accepted, and further studies are required to confirm these hypotheses.…”

Section: Genetics Of Ushmentioning

confidence: 99%

Usher Syndrome

Castiglione

Möller

2022

Audiology Research

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Usher syndrome (USH) is the most common genetic condition responsible for combined loss of hearing and vision. Balance disorders and bilateral vestibular areflexia are also observed in some cases. The syndrome was first described by Albrecht von Graefe in 1858, but later named by Charles Usher, who presented a large number of cases with hearing loss and retinopathy in 1914. USH has been grouped into three main clinical types: 1, 2, and 3, which are caused by mutations in different genes and are further divided into different subtypes. To date, nine causative genes have been identified and confirmed as responsible for the syndrome when mutated: MYO7A, USH1C, CDH23, PCDH15, and USH1G (SANS) for Usher type 1; USH2A, ADGRV1, and WHRN for Usher type 2; CLRN1 for Usher type 3. USH is inherited in an autosomal recessive pattern. Digenic, bi-allelic, and polygenic forms have also been reported, in addition to dominant or nonsyndromic forms of genetic mutations. This narrative review reports the causative forms, diagnosis, prognosis, epidemiology, rehabilitation, research, and new treatments of USH.

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New clinical and molecular evidence linking mutations in ARSG to Usher syndrome type IV

Cited by 33 publications

References 37 publications

Usher Syndrome: Genetics of a Human Ciliopathy

Usher Syndrome: Genetics of a Human Ciliopathy

An Engineered sgsh Mutant Zebrafish Recapitulates Molecular and Behavioural Pathobiology of Sanfilippo Syndrome A/MPS IIIA

Usher Syndrome

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