Outcomes of identifying enlarged vestibular aqueduct (Mondini malformation) related gene mutation in Mongolian people
- VernacularTitle:Дунгийн гажиг хөгжил (Мондини хам шинж)-тэй Монгол хүнд генийн мутацийг тогтоосон үр дүн
- Author:
Jargalkhuu E
1
;
Tserendulam B
2
;
Maralgoo J
2
;
Zaya M
2
;
Enkhtuya B
2
;
Ulzii B
2
;
Ynjinlhkam E
2
;
Chuluun-Erdene Ts
2
;
Chen-Chi Wu
3
;
Cheng-Yu Tsai
3
;
Yin-Hung Lin
3
;
Yi-Hsin Lin
3
;
Yen-Hui Chan
3
;
Chuan-Jen Hsu
3
;
Wei-Chung Hsu
3
;
Pei-Lung Chen
3
Author Information
1. Mongolian National University of Medical Science, School of Medicine,Department of Otorhinolaryngology
2. EMJJ ENT-Uni Hosptal
3. National Taiwan University Hospital, Department of Otorhinolaryngology
- Publication Type:Journal Article
- Keywords:
SNHI-Sensorineural hearing impairment, HHI-hereditary hearing impairment, WES-Whole exome sequencing, DFNB, SLC26A4
- From:
Mongolian Journal of Health Sciences
2025;87(3):8-15
- CountryMongolia
- Language:Mongolian
-
Abstract:
Background:Hearing loss (HL) is one of the most common sensory disorders,
affecting over 5-8% of the world's population. Approximately half of HL cases are
attributed to genetic factors. In hereditary deafness, about 75-80% is inherited
through autosomal recessive inheritance, and common pathogenic genes include
GJB2 and SLC26A4. Pathogenic variants in the SLC26A4gene are the leading
cause of hereditary hearing loss in humans, second only to the GJB2 gene. Variants in the SLC26A4gene cause hearing loss, which can be non-syndromic autosomal recessive deafness (DFNB4, OMIM #600791) associated with enlarged
vestibular aqueduct (EVA) or Pendred syndrome (Pendred, OMIM #605646).
DFNB4 is characterized by sensorineural hearing loss combined with EVA or less
common cochlear malformation defect. Pendred syndrome is characterized by bilateral sensorineural hearing loss with EVA and an iodine defect that can lead to
thyroid goiter. Currently, it is known that EVA is associated with variants in the
SLC26A4 gene and is a penetrant feature of SLC26A4-related HL. Predominant
mutations in these genes differ significantly across populations. For instance, predominant SLC26A4 mutations differ among populations, including p.T416P and
c.1001G>A in Caucasians, p.H723R in Japanese and Koreans, and c.919-2A>G
in Han Taiwanese and Han Chinese. On the other hand, there has been no study
of hearing loss related to SLC26A4 gene variants among Mongolians, which is the
basis of our research.
Aim:We aimed to identify the characteristics of the SLC26A4 gene variants in
Mongolian people with Enlarged vestibular aqueduct and Mondini malformation.
Materials and Methods:In 2022-2024, We included 13 people with hearing loss
and enlarged vestibular aqueduct, incomplete cochlea (1.5 turns of the cochlea
with cystic apex- incomplete partition type II- Mondini malformation) were examined by CT scan of the temporal bone in our study. WES (Whole exome sequencing) analysis was performed in the Genetics genetic-laboratory of the National
Taiwan University Hospital.
Results:Genetic analysis revealed 26 confirmed pathogenic variants of bi-allelic
SLC26A4 gene of 8 different types in 13 cases, and c.919-2A>G variant was dominant with 46% (12/26) in allele frequency, and c.2027T>A (p.L676Q) variant 19%
(5/26), c.1318A>T(p.K440X) variant 11% (3/26), c.1229C>T (p.T410M) variant 8%
(2/26) ) , c.716T>A (p.V239D), c.281C>T (p.T94I), c.1546dupC, and c.1975G>C
(p.V659L) variants were each 4% (1/26)- revealed. Two male children, 11 years
old (SLC26A4: c.919-2A>G) and 7 years old (SLC26A4: c.919-2A>G:, SLC26A4:
c.2027T>A (p.L676Q))had history of born normal hearing and progressive hearing
loss.
Conclusions:1. 26 variants of bi-allelic SLC26A4 gene mutation were detected
in Mongolian people with EVA and Mondini malformation, and c.919-2A>G was
the most dominant allele variant, and rare variants such as c.1546dupC, c.716T>A
(p.V239D) were detected.
2. Our study shows that whole-exome sequencing (WES) can identify gene
mutations that are not detected by polymerase chain reaction (PCR) or NGS analysis.
- Full text:20250523171817776948-15.pdf
