Novel <i>ABHD12</i> Mutations in PHARC Patients

Yoshimura, Hidekane; Hashimoto, Takao; Murata, Toshinori; Fukushima, Kunihiro; Sugaya, Akiko; Nishio, Shin‐ya; Usami, Shin Ichi

doi:10.1177/0003489415574513

Cited by 24 publications

(18 citation statements)

References 10 publications

(15 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When ABHD12 activity is absent, the Purkinje neurons are constantly stimulated by the accumulated lyso-PS, resulting in deregulated cerebellar function [19]. Consistent with previous studies, we found that hearing loss was present in the majority of patients in childhood/early adolescence [1,10,20,21]. To date, it remains unclear where ABHD12 localizes and interacts in the inner ear, which is crucial for determining the cause of hearing loss in patients with PHARC syndrome.…”

Section: Discussionsupporting

confidence: 89%

The Phenotypic Spectrum of Patients with PHARC Syndrome Due to Variants in ABHD12: An Ophthalmic Perspective

Nguyen

Almushattat

Strubbe

et al. 2021

Genes

View full text Add to dashboard Cite

This study investigated the phenotypic spectrum of PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa and early-onset cataract) syndrome caused by biallelic variants in the ABHD12 gene. A total of 15 patients from 12 different families were included, with a mean age of 36.7 years (standard deviation [SD] ± 11.0; range from 17.5 to 53.9) at the most recent examination. The presence and onset of neurological, audiological and ophthalmic symptoms were variable, with no evident order of symptom appearance. The mean best-corrected visual acuity was 1.1 logMAR (SD ± 0.9; range from 0.1 to 2.8; equivalent to 20/250 Snellen) and showed a trend of progressive decline. Different types of cataract were observed in 13 out of 15 patients (87%), which also included congenital forms of cataract. Fundus examination revealed macular involvement in all patients, ranging from alterations of the retinal pigment epithelium to macular atrophy. Intraretinal spicular hyperpigmentation was observed in 7 out of 15 patients (47%). From an ophthalmic perspective, clinical manifestations in patients with PHARC demonstrate variability with regard to their onset and severity. Given the variable nature of PHARC, an early multidisciplinary assessment is recommended to assess disease severity.

show abstract

Section: Discussionsupporting

confidence: 89%

The Phenotypic Spectrum of Patients with PHARC Syndrome Due to Variants in ABHD12: An Ophthalmic Perspective

Nguyen

Almushattat

Strubbe

et al. 2021

Genes

View full text Add to dashboard Cite

show abstract

“…Mutations of ABHD12 have been reported in PHARC syndrome, which is characterized by a combination of polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and earlyonset cataracts. However, several biallelic pathogenic variants have been identified in patients clinically diagnosed with USH3-like symptoms or an autosomal recessive nonsyndromic form of retinal degeneration (Eisenberger et al 2012;Nishiguchi et al 2014;Sun et al 2018;Yoshimura et al 2015). One major problem with these studies is that they do not usually include neurological results for the patients, potentially leading to the misdiagnosis of their condition as USH3.…”

Section: Hars (Histidyl-trna Synthetase)mentioning

confidence: 99%

The genetic and phenotypic landscapes of Usher syndrome: from disease mechanisms to a new classification

Delmaghani

El-Amraoui

2022

Hum Genet

View full text Add to dashboard Cite

Usher syndrome (USH) is the most common cause of deaf–blindness in humans, with a prevalence of about 1/10,000 (~ 400,000 people worldwide). Cochlear implants are currently used to reduce the burden of hearing loss in severe-to-profoundly deaf patients, but many promising treatments including gene, cell, and drug therapies to restore the native function of the inner ear and retinal sensory cells are under investigation. The traditional clinical classification of Usher syndrome defines three major subtypes—USH1, 2 and 3—according to hearing loss severity and onset, the presence or absence of vestibular dysfunction, and age at onset of retinitis pigmentosa. Pathogenic variants of nine USH genes have been initially reported: MYO7A, USH1C, PCDH15, CDH23, and USH1G for USH1, USH2A, ADGRV1, and WHRN for USH2, and CLRN1 for USH3. Based on the co-occurrence of hearing and vision deficits, the list of USH genes has been extended to few other genes, but with limited supporting information. A consensus on combined criteria for Usher syndrome is crucial for the development of accurate diagnosis and to improve patient management. In recent years, a wealth of information has been obtained concerning the properties of the Usher proteins, related molecular networks, potential genotype–phenotype correlations, and the pathogenic mechanisms underlying the impairment or loss of hearing, balance and vision. The advent of precision medicine calls for a clear and more precise diagnosis of Usher syndrome, exploiting all the existing data to develop a combined clinical/genetic/network/functional classification for Usher syndrome.

show abstract

“…Its substrates include endocannabinoid transmitter 2-arachidonylglycerol (2-AG) and signaling lipids (lysophosphatidylserines, LPS) (83,114). Both Eisenberger et al and Yoshimura et al identified bi-allelic ABHD12 pathogenic variants in patients initially presenting with USH3-like symptoms (49,57). However, it is important to note that both sets of authors ultimately diagnosed the patients with a different condition comprising polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and early-onset cataract (PHARC).…”

Section: Ultra-rare Ush Genesmentioning

confidence: 99%

Atypical and ultra-rare Usher syndrome: a review

Hufnagel

Friedman

Turriff

et al. 2020

Ophthalmic Genetics

View full text Add to dashboard Cite

Usher syndrome has classically been described as a combination of hearing loss and rod-cone dystrophy; vestibular dysfunction is present in many patients. Three distinct clinical subtypes were documented in the late 1970s. Genotyping efforts have led to the identification of several genes associated with the disease. Recent literature has seen multiple publications referring to "atypical" Usher syndrome presentations. This manuscript reviews the molecular etiology of Usher syndrome, highlighting rare presentations and molecular causes. Reports of "atypical" disease are summarized noting the wide discrepancy in the spectrum of phenotypic deviations from the classical presentation. Guidelines for establishing a clear nomenclature system are suggested.

show abstract

Novel ABHD12 Mutations in PHARC Patients

Cited by 24 publications

References 10 publications

The Phenotypic Spectrum of Patients with PHARC Syndrome Due to Variants in ABHD12: An Ophthalmic Perspective

The Phenotypic Spectrum of Patients with PHARC Syndrome Due to Variants in ABHD12: An Ophthalmic Perspective

The genetic and phenotypic landscapes of Usher syndrome: from disease mechanisms to a new classification

Atypical and ultra-rare Usher syndrome: a review

Contact Info

Product

Resources

About