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Novel compound heterozygous ATP6V1B1 mutations in a Chinese child patient with primary distal renal tubular acidosis: a case report.
BMC Nephrol 2018; 19(1):364BN

Abstract

BACKGROUND

Distal renal tubular acidosis (dRTA) is a heterogeneous disorder characterized by normal anion gap metabolic acidosis. Autosomal recessive dRTA is usually caused by mutations occurring in ATP6V1B1 and ATP6V0A4 genes,encoding subunits B1 and a4 of apical H+-ATPase, respectively. The heterogeneous clinical manifestations of dRTA have been described in different ethnic groups harboring distinct mutations. Most of the reported cases are from Europe and Africa. At present, the prevalence of primary dRTA is still poorly elucidated in Chinese population.

CASE PRESENTATION

A 2-year and six-month-old female patient was hospitalized because of recurrent hypokalemia, hyperchloremic metabolic acidosis and growth retardation. Laboratory investigations presented a normal anion gap hyperchloremic metabolic acidosis, hypokalemia, and inappropriate alkaline urine. Renal ultrasound indicated bilateral nephrocalcinosis. Bilateral sensorineural hearing loss (SNHL) was confirmed with moderately severe (45 dB) on the left ear and severe (80 dB) on the right ear, which was accompanied with enlarged vestibular aqueduct (EVA) on both sides. According to these findings, a diagnosis of dRTA was made. To identify the pathogenic gene mutation, all coding regions of ATP6V1B1 and ATP6V0A4 gene, including intron-exon boundaries, were analyzed using PCR followed by direct sequence analysis. The splicing variants were verified in peripheral blood leucocytes of the patient by RT-PCR. As a result, two novel heterozygous mutations in ATP6V1B1 were identified in the child. One mutation was a successive 2-nucleotide deletion in exon 2(c.133-134delTG), which caused a marked nonsense mediated mRNA decay. The other was a guanine to adenine substitution of the first nucleotide of intron 8(c.785 + 1 G > A), which led to the exclusion of exon 8. After treatment with sodium citrate, potassium citrateand citric acid, metabolic acidosis and hypokalemia were corrected, but her hearing decreased gradually during the 2 years and had to accept the use of bilateral hearing aids.

CONCLUSIONS

We described two novel dRTA associated mutations in ATP6V1B1 identified in a Chinese child patient accompanying with SNHL and EVA. Our study will help to expand the understanding of this rare disease in Chinese population.

Authors+Show Affiliations

Central Laboratory, The Affiliated Hospital of Qingdao University, 1677 Wutaishan Road, Qingdao, 266555, China.Central Laboratory, The Affiliated Hospital of Qingdao University, 1677 Wutaishan Road, Qingdao, 266555, China. Department of Nephrology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.Department of Nephrology, Qingdao Branch of Qilu Hospital of Shandong University, Qingdao, Shandong, 266000, People's Republic of China.Central Laboratory, The Affiliated Hospital of Qingdao University, 1677 Wutaishan Road, Qingdao, 266555, China. Department of Nephrology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.Central Laboratory, The Affiliated Hospital of Qingdao University, 1677 Wutaishan Road, Qingdao, 266555, China.Central Laboratory, The Affiliated Hospital of Qingdao University, 1677 Wutaishan Road, Qingdao, 266555, China. lepingshao@163.com. Department of Nephrology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China. lepingshao@163.com. Central Laboratory and Department of Nephrolog, the Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China. lepingshao@163.com.

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30558562

Citation

Zhao, Xiangzhong, et al. "Novel Compound Heterozygous ATP6V1B1 Mutations in a Chinese Child Patient With Primary Distal Renal Tubular Acidosis: a Case Report." BMC Nephrology, vol. 19, no. 1, 2018, p. 364.
Zhao X, Lu J, Gao Y, et al. Novel compound heterozygous ATP6V1B1 mutations in a Chinese child patient with primary distal renal tubular acidosis: a case report. BMC Nephrol. 2018;19(1):364.
Zhao, X., Lu, J., Gao, Y., Wang, X., Lang, Y., & Shao, L. (2018). Novel compound heterozygous ATP6V1B1 mutations in a Chinese child patient with primary distal renal tubular acidosis: a case report. BMC Nephrology, 19(1), p. 364. doi:10.1186/s12882-018-1173-1.
Zhao X, et al. Novel Compound Heterozygous ATP6V1B1 Mutations in a Chinese Child Patient With Primary Distal Renal Tubular Acidosis: a Case Report. BMC Nephrol. 2018 12 17;19(1):364. PubMed PMID: 30558562.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel compound heterozygous ATP6V1B1 mutations in a Chinese child patient with primary distal renal tubular acidosis: a case report. AU - Zhao,Xiangzhong, AU - Lu,Jingru, AU - Gao,Yanxia, AU - Wang,Xiaoling, AU - Lang,Yanhua, AU - Shao,Leping, Y1 - 2018/12/17/ PY - 2017/11/20/received PY - 2018/12/05/accepted PY - 2018/12/19/entrez PY - 2018/12/19/pubmed PY - 2019/10/11/medline KW - ATP6V1B1 gene KW - Distal renal tubular acidosis KW - Enlarged vestibular aqueduct KW - Sensorineural hearing loss SP - 364 EP - 364 JF - BMC nephrology JO - BMC Nephrol VL - 19 IS - 1 N2 - BACKGROUND: Distal renal tubular acidosis (dRTA) is a heterogeneous disorder characterized by normal anion gap metabolic acidosis. Autosomal recessive dRTA is usually caused by mutations occurring in ATP6V1B1 and ATP6V0A4 genes,encoding subunits B1 and a4 of apical H+-ATPase, respectively. The heterogeneous clinical manifestations of dRTA have been described in different ethnic groups harboring distinct mutations. Most of the reported cases are from Europe and Africa. At present, the prevalence of primary dRTA is still poorly elucidated in Chinese population. CASE PRESENTATION: A 2-year and six-month-old female patient was hospitalized because of recurrent hypokalemia, hyperchloremic metabolic acidosis and growth retardation. Laboratory investigations presented a normal anion gap hyperchloremic metabolic acidosis, hypokalemia, and inappropriate alkaline urine. Renal ultrasound indicated bilateral nephrocalcinosis. Bilateral sensorineural hearing loss (SNHL) was confirmed with moderately severe (45 dB) on the left ear and severe (80 dB) on the right ear, which was accompanied with enlarged vestibular aqueduct (EVA) on both sides. According to these findings, a diagnosis of dRTA was made. To identify the pathogenic gene mutation, all coding regions of ATP6V1B1 and ATP6V0A4 gene, including intron-exon boundaries, were analyzed using PCR followed by direct sequence analysis. The splicing variants were verified in peripheral blood leucocytes of the patient by RT-PCR. As a result, two novel heterozygous mutations in ATP6V1B1 were identified in the child. One mutation was a successive 2-nucleotide deletion in exon 2(c.133-134delTG), which caused a marked nonsense mediated mRNA decay. The other was a guanine to adenine substitution of the first nucleotide of intron 8(c.785 + 1 G > A), which led to the exclusion of exon 8. After treatment with sodium citrate, potassium citrateand citric acid, metabolic acidosis and hypokalemia were corrected, but her hearing decreased gradually during the 2 years and had to accept the use of bilateral hearing aids. CONCLUSIONS: We described two novel dRTA associated mutations in ATP6V1B1 identified in a Chinese child patient accompanying with SNHL and EVA. Our study will help to expand the understanding of this rare disease in Chinese population. SN - 1471-2369 UR - https://www.unboundmedicine.com/medline/citation/30558562/Novel_compound_heterozygous_ATP6V1B1_mutations_in_a_Chinese_child_patient_with_primary_distal_renal_tubular_acidosis:_a_case_report_ L2 - https://www.biomedcentral.com/1471-2369/19/364 DB - PRIME DP - Unbound Medicine ER -