Novel KCNJ16 variants identified in a Chinese patient with hypokalemic metabolic acidosis
Abstract Background Biallelic pathogenic variants in the KCNJ16 gene result in hypokalemic tubulopathy and deafness (HKTD) (MIM #619406), which is a rare autosomal recessive disease characterized by hypokalemic tubulopathy with renal salt wasting, disturbed acid–base homeostasis, and sensorineural d...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-11-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.2238 |
| _version_ | 1797610471727038464 |
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| author | Jianxiong Chen Youqing Fu Yan Sun Xinlong Zhou Qingming Wang Cong Li Haiming Yuan |
| author_facet | Jianxiong Chen Youqing Fu Yan Sun Xinlong Zhou Qingming Wang Cong Li Haiming Yuan |
| author_sort | Jianxiong Chen |
| collection | DOAJ |
| description | Abstract Background Biallelic pathogenic variants in the KCNJ16 gene result in hypokalemic tubulopathy and deafness (HKTD) (MIM #619406), which is a rare autosomal recessive disease characterized by hypokalemic tubulopathy with renal salt wasting, disturbed acid–base homeostasis, and sensorineural deafness. Currently, nine individuals with HKTD have been reported, and seven pathogenic variants in KCNJ16 have been revealed. Methods A 5‐year‐6‐month‐old Chinese female patient displayed hypokalemic metabolic acidosis, salt wasting, renin‐angiotensin‐aldosterone system (RAAS) activation, arrhythmia, myocardial damage, cardiogenic shock and secondary diffuse brain oedema. Trio‐based whole‐exome sequencing (WES) was applied to detect the genetic cause. Results Novel compound heterozygous variants, c.190A>C (p.Thr64Pro) and c.628C>G (p.His210Asp), in KCNJ16 were detected in the patient, and these variants were inherited from the patient's mother and father, respectively. Then, we systematically reviewed the available clinical manifestations of individuals with HKTD. We found that HKTD patients are at risk of cardiogenic shock and secondary diffuse brain oedema, which urges clinicians to make early diagnoses with prompt treatments. Conclusion These findings expand the variant spectrum of KCNJ16, enrich the clinical characteristics of HKTD, and provide a solid base for the genetic counseling, diagnosis and treatment of this condition. |
| first_indexed | 2024-03-11T06:14:50Z |
| format | Article |
| id | doaj.art-daf6c71dfdee49ee9ed4a6bdc20f6492 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-11T06:14:50Z |
| publishDate | 2023-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-daf6c71dfdee49ee9ed4a6bdc20f64922023-11-17T12:23:28ZengWileyMolecular Genetics & Genomic Medicine2324-92692023-11-011111n/an/a10.1002/mgg3.2238Novel KCNJ16 variants identified in a Chinese patient with hypokalemic metabolic acidosisJianxiong Chen0Youqing Fu1Yan Sun2Xinlong Zhou3Qingming Wang4Cong Li5Haiming Yuan6Dongguan Maternal and Child Health Care Hospital Dongguan ChinaDongguan Maternal and Child Health Care Hospital Dongguan ChinaDongguan Maternal and Child Health Care Hospital Dongguan ChinaDongguan Maternal and Child Health Care Hospital Dongguan ChinaDongguan Maternal and Child Health Care Hospital Dongguan ChinaDongguan Maternal and Child Health Care Hospital Dongguan ChinaDongguan Maternal and Child Health Care Hospital Dongguan ChinaAbstract Background Biallelic pathogenic variants in the KCNJ16 gene result in hypokalemic tubulopathy and deafness (HKTD) (MIM #619406), which is a rare autosomal recessive disease characterized by hypokalemic tubulopathy with renal salt wasting, disturbed acid–base homeostasis, and sensorineural deafness. Currently, nine individuals with HKTD have been reported, and seven pathogenic variants in KCNJ16 have been revealed. Methods A 5‐year‐6‐month‐old Chinese female patient displayed hypokalemic metabolic acidosis, salt wasting, renin‐angiotensin‐aldosterone system (RAAS) activation, arrhythmia, myocardial damage, cardiogenic shock and secondary diffuse brain oedema. Trio‐based whole‐exome sequencing (WES) was applied to detect the genetic cause. Results Novel compound heterozygous variants, c.190A>C (p.Thr64Pro) and c.628C>G (p.His210Asp), in KCNJ16 were detected in the patient, and these variants were inherited from the patient's mother and father, respectively. Then, we systematically reviewed the available clinical manifestations of individuals with HKTD. We found that HKTD patients are at risk of cardiogenic shock and secondary diffuse brain oedema, which urges clinicians to make early diagnoses with prompt treatments. Conclusion These findings expand the variant spectrum of KCNJ16, enrich the clinical characteristics of HKTD, and provide a solid base for the genetic counseling, diagnosis and treatment of this condition.https://doi.org/10.1002/mgg3.2238cardiogenic shockhypokalemic metabolic acidosishypokalemic tubulopathy and deafnessKCNJ16 |
| spellingShingle | Jianxiong Chen Youqing Fu Yan Sun Xinlong Zhou Qingming Wang Cong Li Haiming Yuan Novel KCNJ16 variants identified in a Chinese patient with hypokalemic metabolic acidosis Molecular Genetics & Genomic Medicine cardiogenic shock hypokalemic metabolic acidosis hypokalemic tubulopathy and deafness KCNJ16 |
| title | Novel KCNJ16 variants identified in a Chinese patient with hypokalemic metabolic acidosis |
| title_full | Novel KCNJ16 variants identified in a Chinese patient with hypokalemic metabolic acidosis |
| title_fullStr | Novel KCNJ16 variants identified in a Chinese patient with hypokalemic metabolic acidosis |
| title_full_unstemmed | Novel KCNJ16 variants identified in a Chinese patient with hypokalemic metabolic acidosis |
| title_short | Novel KCNJ16 variants identified in a Chinese patient with hypokalemic metabolic acidosis |
| title_sort | novel kcnj16 variants identified in a chinese patient with hypokalemic metabolic acidosis |
| topic | cardiogenic shock hypokalemic metabolic acidosis hypokalemic tubulopathy and deafness KCNJ16 |
| url | https://doi.org/10.1002/mgg3.2238 |
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