De novo mutation of the connexin 26 gene associated with dominant non-syndromic sensorineural hearing loss

2001 ◽  
Vol 108 (3) ◽  
pp. 269-270 ◽  
Author(s):  
Andreas R Janecke ◽  
Doris Nekahm ◽  
Judith Löffler ◽  
Almut Hirst-Stadlmann ◽  
Thomas Müller ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
De Novo ◽  
Sensorineural Hearing ◽  
De Novo Mutation ◽  
Connexin 26

scholarly journals SLC12A2 variants cause a neurodevelopmental disorder or cochleovestibular defect

Brain ◽  
2020 ◽  
Vol 143 (8) ◽  
pp. 2380-2387 ◽  
Author(s):  
Alisdair McNeill ◽  
Emanuela Iovino ◽  
Luke Mansard ◽  
Christel Vache ◽  
David Baux ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Developmental Disorders ◽  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Sensorineural Deafness ◽  
Sensorineural Hearing ◽  
De Novo Mutation ◽  
Xenopus Laevis Oocytes ◽  
De Novo Mutations

Abstract The SLC12 gene family consists of SLC12A1–SLC12A9, encoding electroneutral cation-coupled chloride co-transporters. SCL12A2 has been shown to play a role in corticogenesis and therefore represents a strong candidate neurodevelopmental disorder gene. Through trio exome sequencing we identified de novo mutations in SLC12A2 in six children with neurodevelopmental disorders. All had developmental delay or intellectual disability ranging from mild to severe. Two had sensorineural deafness. We also identified SLC12A2 variants in three individuals with non-syndromic bilateral sensorineural hearing loss and vestibular areflexia. The SLC12A2 de novo mutation rate was demonstrated to be significantly elevated in the deciphering developmental disorders cohort. All tested variants were shown to reduce co-transporter function in Xenopus laevis oocytes. Analysis of SLC12A2 expression in foetal brain at 16–18 weeks post-conception revealed high expression in radial glial cells, compatible with a role in neurogenesis. Gene co-expression analysis in cells robustly expressing SLC12A2 at 16–18 weeks post-conception identified a transcriptomic programme associated with active neurogenesis. We identify SLC12A2 de novo mutations as the cause of a novel neurodevelopmental disorder and bilateral non-syndromic sensorineural hearing loss and provide further data supporting a role for this gene in human neurodevelopment.

V37I connexin 26 allele in patients with sensorineural hearing loss: Evidence of its pathogenicity

2006 ◽  
Vol 140A (22) ◽  
pp. 2394-2400 ◽  
Author(s):  
C. Huculak ◽  
H. Bruyere ◽  
T. N. Nelson ◽  
F. K. Kozak ◽  
S. Langlois
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Sensorineural Hearing ◽  
Connexin 26

Analysis of Gjb2 (Connexin 26) Mutation in Patients with Congenital Non-Syndromic Sensorineural Hearing Loss

2014 ◽  
Vol 52 (1) ◽  
pp. 1-6
Author(s):  
Emin Kaskalan ◽  
Ebru Etem Onalan ◽  
Irfan Kaygusuz ◽  
Turgut Karlidag ◽  
Erol Keles ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Sensorineural Hearing ◽  
Connexin 26

scholarly journals Auditory Neuropathy as the Initial Phenotype for Patients With ATP1A3 c.2452 G > A: Genotype–Phenotype Study and CI Management

2021 ◽  
Vol 9 ◽  
Author(s):  
Wenjia Wang ◽  
Jin Li ◽  
Lan Lan ◽  
Linyi Xie ◽  
Fen Xiong ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Pure Tone ◽  
De Novo ◽  
Pure Tone Audiometry ◽  
Auditory Neuropathy ◽  
Neurological Symptoms ◽  
Sensorineural Hearing ◽  
Auditory Brainstem Responses ◽  
Capos Syndrome

Objective: The objective of this study is to analyze the genotype–phenotype correlation of patients with auditory neuropathy (AN), which is a clinical condition featuring normal cochlear responses and abnormal neural responses, and ATP1A3 c.2452 G > A (p.E818K), which has been generally recognized as a genetic cause of cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) syndrome.Methods: Four patients diagnosed as AN by clinical evaluation and otoacoustic emission and auditory brainstem responses were recruited and analyzed by next-generation sequencing to identify candidate disease-causing variants. Sanger sequencing was performed on the patients and their parents to verify the results, and short tandem repeat-based testing was conducted to confirm the biological relationship between the parents and the patients. Furthermore, cochlear implantation (CI) was performed in one AN patient to reconstruct hearing.Results: Four subjects with AN were identified to share a de novo variant, p.E818K in the ATP1A3 gene. Except for the AN phenotype, patients 1 and 2 exhibited varying degrees of neurological symptoms, implying that they can be diagnosed as CAPOS syndrome. During the 15 years follow-up of patient 1, we observed delayed neurological events and progressive bilateral sensorineural hearing loss in pure tone threshold (pure tone audiometry, PTA). Patient 2 underwent CI on his left ear, and the result was poor. The other two patients (patient 3 and patient 4, who were 8 and 6 years old, respectively) denied any neurological symptoms.Conclusion:ATP1A3 p.E818K has rarely been documented in the Chinese AN population. Our study confirms that p.E818K in the ATP1A3 gene is a multiethnic cause of AN in Chinese individuals. Our study further demonstrates the significance of genetic testing for this specific mutation for identifying the special subtype of AN with somewhat favorable CI outcome and offers a more accurate genetic counseling about the specific de novo mutation.

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