Genotype-Phenotype Correlation for Predicting Cochlear Implant Outcome: Current Challenges and Opportunities

Eshraghi, Adrien A.; Polineni, Sai; Davies, Camron; Shahal, David; Mittal, Jeenu; Al-Zaghal, Zaid; Sinha, Rahul; Jindal, Urmi; Mittal, Rahul

doi:10.3389/fgene.2020.00678

Cited by 21 publications

(16 citation statements)

References 164 publications

(240 reference statements)

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“…Spiral ganglion neurons are necessary to transmit a CI-initiated electrical stimulation to the brainstem. Nevertheless, two recent reviews on this subject point to individuals with auditory neuropathy spectrum disorders (ANSD) who do benefit from cochlear implants (Eshraghi et al 2020;Shearer and Hansen 2019). Benefit from a CI depends on the site and magnitude of the physiological lesion.…”

Section: Rna-seq Of Perrault Syndrome Genes Demonstrates Prominent Expression In Spiral Ganglion Neuronsmentioning

confidence: 99%

New insights into Perrault syndrome, a clinically and genetically heterogeneous disorder

et al. 2021

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Hearing loss and impaired fertility are common human disorders each with multiple genetic causes. Sometimes deafness and impaired fertility, which are the hallmarks of Perrault syndrome, co-occur in a person. Perrault syndrome is inherited as an autosomal recessive disorder characterized by bilateral mild to severe childhood sensorineural hearing loss with variable age of onset in both sexes and ovarian dysfunction in females who have a 46, XX karyotype. Since the initial clinical description of Perrault syndrome 70 years ago, the phenotype of some subjects may additionally involve developmental delay, intellectual deficit and other neurological disabilities, which can vary in severity in part dependent upon the genetic variants and the gene involved. Here, we review the molecular genetics and clinical phenotype of Perrault syndrome and focus on supporting evidence for the eight genes (CLPP, ERAL1, GGPS1, HARS2, HSD17B4, LARS2, RMND1, TWNK) associated with Perrault syndrome. Variants of these eight genes only account for approximately half of the individuals with clinical features of Perrault syndrome where the molecular genetic base remains under investigation. Additional environmental etiologies and novel Perrault disease-associated genes remain to be identified to account for unresolved cases. We also report a new genetic variant of CLPP, computational structural insight about CLPP and single cell RNAseq data for eight reported Perrault syndrome genes suggesting a common cellular pathophysiology for this disorder. Some unanswered questions are raised to kindle future research about Perrault syndrome.

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Section: Rna-seq Of Perrault Syndrome Genes Demonstrates Prominent Expression In Spiral Ganglion Neuronsmentioning

confidence: 99%

New insights into Perrault syndrome, a clinically and genetically heterogeneous disorder

et al. 2021

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“…Accumulating evidence reveals that CI outcomes correlate closely with the etiologies of pediatric SNHL [ 12 , 13 , 14 , 15 ]. We recently demonstrated that comprehensive history-taking, genetic examinations, and imaging studies were useful in addressing the etiological heterogeneity of pediatric ANSD and could help obtain information regarding the causes of ANSD in 75% of the patients [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Cochlear Implantation Outcomes in Patients with Auditory Neuropathy Spectrum Disorder of Genetic and Non-Genetic Etiologies: A Multicenter Study

Lin

et al. 2022

Biomedicines

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With diverse etiologies and clinical features, the management of pediatric auditory neuropathy spectrum disorder (ANSD) is often challenging, and the outcomes of cochlear implants (CIs) are variable. This study aimed to investigate CI outcomes in pediatric patients with ANSD of different etiologies. Thirty-six children with ANSD who underwent cochlear implantation between 2001 and 2021 were included. Comprehensive etiological analyses were conducted, including a history review, next-generation sequencing-based genetic examinations, and imaging studies using high-resolution computed tomography and magnetic resonance imaging. Serial behavioral and speech audiometry were performed before and after surgery, and the outcomes with CI were evaluated using the Categories of Auditory Performance (CAP) and Speech Intelligibility Rating (SIR) scores. By etiology, 18, 1, 1, and 10 patients had OTOF-related, WFS1-related, OPA1-related, and cochlear nerve deficiency (CND)-related ANSD, respectively. Six patients had no definite etiology. The average CI-aided behavioral threshold was 28.3 ± 7.8 dBHL, and those with CND-related ANSD were significantly worse than OTOF-related ANSD. The patients’ median CAP and SIR scores were 6 and 4, respectively. Favorable CI outcomes were observed in patients with certain etiologies of ANSD, particularly those with OTOF (CAP/SIR scores 5–7/2–5), WFS1 (CAP/SIR score 6/5), and OPA1 variants (CAP/SIR score 7/5). Patients with CND had suboptimal CI outcomes (CAP/SIR scores 2–6/1–3). Identifying the etiologies in ANSD patients is crucial before surgery and can aid in predicting prognoses.

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“…For example, it has been reported that patients with DFNB2 have been subsequently investigated and diagnosed for mild RP. Nevertheless, “age at surgery” is the most important prognostic factor [ 58 , 59 , 60 ]. Ineligible cases till surgery or poor outcomes of CIs may benefit from tactile and sign language [ 61 ].…”

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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Genotype-Phenotype Correlation for Predicting Cochlear Implant Outcome: Current Challenges and Opportunities

Cited by 21 publications

References 164 publications

New insights into Perrault syndrome, a clinically and genetically heterogeneous disorder

New insights into Perrault syndrome, a clinically and genetically heterogeneous disorder

Cochlear Implantation Outcomes in Patients with Auditory Neuropathy Spectrum Disorder of Genetic and Non-Genetic Etiologies: A Multicenter Study

Usher Syndrome

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