Usher Syndrome

Castiglione, Alessandro; Möller, Claes

doi:10.3390/audiolres12010005

Cited by 44 publications

(75 citation statements)

References 118 publications

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“…Hence, the 11 participating children should be a representative sample for alleged nonsyndromic nonprofound congenital SNHL. The term “alleged nonsyndromic” is used as the medical files did not reveal any syndromic disease (that only can be ruled out entirely by comprehensive genetic testing (e.g., [ 20 , 21 ])) for the 11 otherwise healthy participating subjects, see Table I in [ 11 ]. Seven males (subjects no.…”

Section: Methodsmentioning

confidence: 99%

Congenital Nonprofound Bilateral Sensorineural Hearing Loss in Children: Comprehensive Characterization of Auditory Function and Hearing Aid Benefit

et al. 2022

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A prospective cross-sectional design was used to characterize congenital bilateral sensorineural hearing loss (SNHL). The underlying material of >30,000 consecutively screened newborns comprised 11 subjects with nonprofound, alleged nonsyndromic, SNHL. Comprehensive audiological testing was performed at ≈11 years of age. Results showed symmetrical sigmoid-like median pure-tone thresholds (PTTs) reaching 50–60 dB HL. The congenital SNHL revealed recruitment, increased upward spread of masking, distortion product otoacoustic emission (DPOAE) dependent on PTT (≤60 dB HL), reduced auditory brainstem response (ABR) amplitude, and normal magnetic resonance imaging. Unaided recognition of speech in spatially separate competing speech (SCS) deteriorated with increasing uncomfortable loudness level (UCL), plausibly linked to reduced afferent signals. Most subjects demonstrated hearing aid (HA) benefit in a demanding laboratory listening situation. Questionnaires revealed HA benefit in real-world listening situations. This functional characterization should be important for the outline of clinical guidelines. The distinct relationship between DPOAE and PTT, up to the theoretical limit of cochlear amplification, and the low ABR amplitude remain to be elucidated. The significant relation between UCL and SCS has implications for HA-fitting. The fitting of HAs based on causes, mechanisms, and functional characterization of the SNHL may be an individualized intervention approach and deserves future research.

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Section: Methodsmentioning

confidence: 99%

Congenital Nonprofound Bilateral Sensorineural Hearing Loss in Children: Comprehensive Characterization of Auditory Function and Hearing Aid Benefit

et al. 2022

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“…Usher syndrome (USH) is a genetic disorder combining various degrees of sensorineural hearing impairment with a gradual vision loss caused by retinitis pigmentosa (RP) ( Boughman et al, 1983 ; Fuster-García et al, 2018 ; Castiglione and Möller, 2022 ). Hearing impairment is mainly due to changes in morphogenesis and stability of stereocilia projections on the cochlear hair cells that mediate sound transduction ( Frolenkov et al, 2004 ; Millán et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Novel Missense and Splice Site Mutations in USH2A, CDH23, PCDH15, and ADGRV1 Are Associated With Usher Syndrome in Lebanon

et al. 2022

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The purpose of this study was to expand the mutation spectrum by searching the causative mutations in nine Lebanese families with Usher syndrome (USH) using whole-exome sequencing. The pathogenicity of candidate mutations was first evaluated according to their frequency, conservation, and in silico prediction tools. Then, it was confirmed via Sanger sequencing, followed by segregation analysis. Finally, a meta-analysis was conducted to calculate the prevalence of USH genes in the Lebanese population. Three missense mutations, two splice site mutations, and one insertion/deletion were detected in eight of the families. Four of these variants were novel: c.5535C > A; p.(Asn1845Lys) in exon 41 of CDH23, c.7130G > A; p.(Arg2377Gln) in exon 32 of ADGRV1, c.11390-1G > A in USH2A, and c.3999–6A > G in PCDH15. All the identified mutations were shown to be likely disease-causing through our bioinformatics analysis and co-segregated with the USH phenotype. The mutations were classified according to the ACMG standards. Finally, our meta-analysis showed that the mutations in ADGRV1, USH2A, and CLRN1 are the most prevalent and responsible for approximately 75% of USH cases in Lebanon. Of note, the frequency USH type 3 showed a relatively high incidence (23%) compared to the worldwide prevalence, which is around 2–4%. In conclusion, our study has broadened the mutational spectrum of USH and showed a high heterogeneity of this disease in the Lebanese population.

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“…Patients with USH are characterized by rod-cone dystrophy, partial-complete sensorineural hearing loss, and a possibility of vestibular dysfunction [ 2 ]. The severity and onset of symptoms depend on the clinical type — Usher type 1 (USH1), attributed to variants in protein coding genes USH1C, CDH23, PCDH15, and USH1G ; Usher type 2 (USH2) from variants in USH2A, ADGRV1, and WHRN ; Usher type 3 (USH3) from CLRN1 [ 3 ]; and atypical Usher syndrome type 4 (USH4) from ARSG [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Case report: novel PCDH15 variant causes usher syndrome type 1F with congenital hearing loss and syndromic retinitis pigmentosa

Chen

Lee²,

Kim

et al. 2022

BMC Ophthalmol

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Background Usher syndrome (USH) is an autosomal recessive disorder primarily responsible for deaf-blindness. Patients with subtype Usher syndrome type 1 (USH1) typically experience congenital sensorineural hearing loss, abnormal vestibular function, and retinitis pigmentosa (RP). Here we present a case of Usher syndrome type 1F (USH1F) with a novel homozygous variant in the calcium-dependent cell-cell adhesion protocadherin-15 (PCDH15) gene. Case presentation Ophthalmic examinations were evaluated over a course of 10 years and the disease-causing variant was identified by whole exome sequencing (WES). Initial and follow-up examination of color fundus photos after 10 years revealed an increase in bone spicule pigment deposits in both eyes. A parafoveal hyper-AF ring in both eyes was shown in fundus autofluorescence (FAF) with a progressive diameter-wise constriction observed over 8 years. Outer nuclear layer (ONL) loss was observed in parafoveal and perifoveal regions of both eyes on spectral domain–optical coherence tomography (SD-OCT). Full-field electroretinography (ffERG) showed extinguished global retinal function. WES identified a novel two-base-pair deletion, c.60_61del (p.Phe21Ter), in the PCDH15 gene, confirming the diagnosis of USH1F. Conclusions We report a novel homozygous PCDH15 pathogenic variant expected to lead to nonsense-mediated decay (NMD) of PCDH15 mRNA. The patient exhibits a loss of function with USH1F, experiencing congenital hearing loss and syndromic RP.

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Usher Syndrome

Cited by 44 publications

References 118 publications

Congenital Nonprofound Bilateral Sensorineural Hearing Loss in Children: Comprehensive Characterization of Auditory Function and Hearing Aid Benefit

Congenital Nonprofound Bilateral Sensorineural Hearing Loss in Children: Comprehensive Characterization of Auditory Function and Hearing Aid Benefit

Novel Missense and Splice Site Mutations in USH2A, CDH23, PCDH15, and ADGRV1 Are Associated With Usher Syndrome in Lebanon

Case report: novel PCDH15 variant causes usher syndrome type 1F with congenital hearing loss and syndromic retinitis pigmentosa

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