Dataset Information

Identification of a Potential Founder Effect of a Novel PDZD7 Variant Involved in Moderate-to-Severe Sensorineural Hearing Loss in Koreans.

ABSTRACT: PDZD7, a PDZ domain-containing scaffold protein, is critical for the organization of Usher syndrome type 2 (USH2) interactome. Recently, biallelic PDZD7 variants have been associated with autosomal-recessive, non-syndromic hearing loss (ARNSHL). Indeed, we identified novel, likely pathogenic PDZD7 variants based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines from Korean families manifesting putative moderate-to-severe prelingual ARNSHL; these were c.490C>T (p.Arg164Trp), c.1669delC (p.Arg557Glyfs*13), and c.1526G>A (p.Gly509Glu), with p.Arg164Trp being a predominantly recurring variant. Given the recurring missense variant (p.Arg164Trp) from our cohort, we compared the genotyping data using six short tandem-repeat (STR) markers within or flanking PDZD7 between four probands carrying p.Arg164Trp and 81 normal-hearing controls. We observed an identical haplotype across three out of six STR genotyping markers exclusively shared by two unrelated hearing impaired probands but not by any of the 81 normal-hearing controls, suggesting a potential founder effect. However, STR genotyping, based on six STR markers, revealed various p.Arg164Trp-linked haplotypes shared by all of the affected subjects. In conclusion, PDZD7 can be an important causative gene for moderate to severe ARNSHL in Koreans. Moreover, at least some, if not all, p.Arg164Trp alleles in Koreans could exert a potential founder effect and arise from diverse haplotypes as a mutational hot spot.

SUBMITTER: Lee SY

PROVIDER: S-EPMC6747409 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Identification of a Potential Founder Effect of a Novel <i>PDZD7</i> Variant Involved in Moderate-to-Severe Sensorineural Hearing Loss in Koreans.

Lee Sang-Yeon SY Han Jin Hee JH Kim Bong Jik BJ Oh Seung Ha SH Lee Seungmin S Oh Doo-Yi DY Choi Byung Yoon BY

International journal of molecular sciences 20190826 17

PDZD7, a PDZ domain-containing scaffold protein, is critical for the organization of Usher syndrome type 2 (USH2) interactome. Recently, biallelic PDZD7 variants have been associated with autosomal-recessive, non-syndromic hearing loss (ARNSHL). Indeed, we identified novel, likely pathogenic <i>PDZD7</i> variants based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines from Korean families manifesting putative moderate-to-severe pre ...[more]

PMID: 31454969

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Project description:IntroductionTo compare inpatient treated patients with idiopathic (ISSNHL) and non-idiopathic sudden sensorineural hearing loss (NISSNHL) regarding frequency, hearing loss, treatment and outcome.MethodsAll 574 inpatient patients (51% male, median age: 60 years) with ISSNHL and NISSNHL, who were treated in federal state Thuringia in 2011 and 2012, were included retrospectively. Univariate and multivariate statistical analyses were performed.ResultsISSNHL was diagnosed in 490 patients (85%), NISSNHL in 84 patients (15%). 49% of these cases had hearing loss due to acute otitis media, 37% through varicella-zoster infection or Lyme disease, 10% through Menière disease and 7% due to other reasons. Patients with ISSNHL and NISSNHL showed no difference between age, gender, side of hearing loss, presence of tinnitus or vertigo and their comorbidities. 45% of patients with ISSNHL and 62% with NISSNHL had an outpatient treatment prior to inpatient treatment (p < 0.001). The mean interval between onset of hearing loss to inpatient treatment was shorter in ISSNHL (7.7 days) than in NISSNHL (8.9 days; p = 0.02). The initial hearing loss of the three most affected frequencies in pure-tone average (3PTAmax) scaled 72.9 dBHL ± 31.3 dBHL in ISSNHL and 67.4 dBHL ± 30.5 dBHL in NISSNHL. In the case of acute otitis media, 3PTAmax (59.7 dBHL ± 24.6 dBHL) was lower than in the case of varicella-zoster infection or Lyme disease (80.11 dBHL ± 34.19 dBHL; p = 0.015). Mean absolute hearing gain (Δ3PTAmaxabs) was 8.1 dB ± 18.8 dB in patients with ISSNHL, and not different in NISSNHL patients with 10.2 dB ± 17.6 dB. A Δ3PTAmaxabs ≥ 10 dB was reached in 34.3% of the patients with ISSNHL and to a significantly higher rate of 48.8% in NISSNHL patients (p = 0.011).ConclusionsISSNHL and NISSNHL show no relevant baseline differences. ISSNHL tends to have a higher initial hearing loss. NISSHNL shows a better outcome than ISSNHL.

Dataset Information

Identification of a Potential Founder Effect of a Novel PDZD7 Variant Involved in Moderate-to-Severe Sensorineural Hearing Loss in Koreans.

Publications

Identification of a Potential Founder Effect of a Novel <i>PDZD7</i> Variant Involved in Moderate-to-Severe Sensorineural Hearing Loss in Koreans.

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