Expanding Genotype–Phenotype Correlation of CLCNKA and CLCNKB Variants Linked to Hearing Loss
Abstract
:1. Introduction
2. Results
2.1. Phenotype
2.2. Exome Sequencing and Data Analysis
2.3. Whole Genome Sequencing and Data Analysis
2.4. Molecular Genetic Analysis
2.5. Phenotype–Genotype Correlation
3. Discussion
4. Materials and Methods
4.1. Participants and Clinical Assessment
4.2. Exome Sequencing and Bioinformatic Analysis
4.3. Whole-Genome Sequencing and Bioinformatic Analysis
4.4. Breakpoint PCR, Digital Droplet PCR, and Sanger Sequencing
4.5. Laboratory Tests
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
SNHL | Sensorineural hearing loss |
WGS | Whole genome sequencing |
MET | Sensory mechanoelectrical transduction |
BS | Bartter syndrome |
ACMG-AMP | American College of Medical Genetics and Genomics/Association for Molecular Pathology |
SVs | Structure variations |
ddPCR | Digital-droplet PCR |
VAF | Variant allele frequency |
CNV | Copy number variations |
gnomAD | Gemone Aggregation Database |
GRCh38 | Human reference genome |
GATK | Genome analysis toolkit |
SNV | Single nucleotide variations |
MAFs | Minor allele frequencies |
KOVA2 | Korean Variant Archive for a reference database of genetic variations in the Korean population |
CADD | Combined Annotation Dependent Depletion |
REVEL | Rare Exome Variant Ensemble Learner |
IGV | Integrative genomics viewer |
USG | Ultrasonography |
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References | Gene | Variant | Zygosity | Age | Clinical Phenotypes | ||
---|---|---|---|---|---|---|---|
Robitaille et al., 2011 [20] | CLCNKB | c.229G>C:p. Ala77Pro | Homozygote | 13-year-old | Batter syndrome type III | Renal phenotype | Severe dehydration secondary to a prolonged diarrhea Chronic metabolic alkalosis Normal renal function |
Hearing phenotype | Sensorineural deafness with a loss of 60–70 dB from 250 to 9 kHz in both ears | ||||||
Nozu et al., 2008 [12] | CLCNKA | c.778C>T:p.Gln260Ter | Heterozygote | 2-year-old | Batter syndrome type IV | Renal phenotype | Polyuria and severe volume depletion Hyponatremia/normal potassium concentration Severe hypokalemia and metabolic alkalosis Acute renal failure. |
Deletion (CLCNKA exon16- CLCNKB intron2) | Heterozygote | ||||||
CLCNKB | IVS17+1G>A: Splicing variant | Heterozygote | Hearing phenotype | Bilateral sensorineural deafness | |||
Deletion (CLCNKA exon16- CLCNKB intron2) | Heterozygote | ||||||
Schlingmann et al., 2004 [9] | CLCNKA | c.240G>C:p.Trp80Cys | Homozygote | 2-month-old | Batter syndrome type IV | Renal phenotype | Polyuria and volume depletion associated with hypokalemia and metabolic alkalosis |
CLCNKB | Whole gene deletion | Homozygote | Hearing phenotype | Bilateral sensorineural deafness |
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Yun, Y.; Park, S.S.; Lee, S.; Seok, H.; Park, S.; Lee, S.-Y. Expanding Genotype–Phenotype Correlation of CLCNKA and CLCNKB Variants Linked to Hearing Loss. Int. J. Mol. Sci. 2023, 24, 17077. https://doi.org/10.3390/ijms242317077
Yun Y, Park SS, Lee S, Seok H, Park S, Lee S-Y. Expanding Genotype–Phenotype Correlation of CLCNKA and CLCNKB Variants Linked to Hearing Loss. International Journal of Molecular Sciences. 2023; 24(23):17077. https://doi.org/10.3390/ijms242317077
Chicago/Turabian StyleYun, Yejin, Sang Soo Park, Soyoung Lee, Heeyoung Seok, Seongyeol Park, and Sang-Yeon Lee. 2023. "Expanding Genotype–Phenotype Correlation of CLCNKA and CLCNKB Variants Linked to Hearing Loss" International Journal of Molecular Sciences 24, no. 23: 17077. https://doi.org/10.3390/ijms242317077