Genotype–Phenotype Analysis in Pediatric Patients with Distal Renal Tubular Acidosis

Autor: Hye Sun Hyun, Myung Hyun Cho, Hyun-Jin Choi, Young Seo Park, Eujin Park, Jae Il Shin, Hee Gyung Kang, Joo H. Lee, Hae Il Cheong
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Candidate gene
lcsh:Diseases of the circulatory (Cardiovascular) system
DNA Mutational Analysis
030232 urology & nephrology
Growth
lcsh:RC870-923
Gastroenterology
0302 clinical medicine
Distal renal tubular acidosis
Anion Exchange Protein 1
Erythrocyte
Chronic kidney disease
lcsh:Dermatology
Child
Kidney Tubules
Distal
Genetic disorder
Acidosis
Renal Tubular
General Medicine
Sensorineural hearing loss
Nephrocalcinosis
Nephrology
Child
Preschool
Female
Cardiology and Cardiovascular Medicine
Mutations
Vacuolar Proton-Translocating ATPases
medicine.medical_specialty
Adolescent
Hearing Loss
Sensorineural
03 medical and health sciences
Internal medicine
Republic of Korea
medicine
Humans
Genetic Association Studies
business.industry
Metabolic acidosis
lcsh:RL1-803
medicine.disease
Growth retardation
lcsh:Diseases of the genitourinary system. Urology
030104 developmental biology
lcsh:RC666-701
Mutation
Age of onset
business
Kidney disease
Zdroj: Kidney & Blood Pressure Research, Vol 43, Iss 2, Pp 513-521 (2018)
ISSN: 1423-0143
1420-4096
Popis: Background/Aims: Primary distal renal tubular acidosis (dRTA) in children is a rare genetic disorder, and three causative mutated genes have been identified: SLC4A1, ATP6V1B1, and ATP6V0A4. We analyzed the prevalence and phenotypic differences of genetic mutations in children with dRTA. Methods: A total of 17 children with dRTA were enrolled in the study. All patients underwent genetic testing for all three candidate genes. Results: Pathogenic mutations, including six novel mutations, were detected in 15 (88.2%) patients: dominant SLC4A1 mutations in ten (58.8%) patients, recessive ATP6V0A4 mutations in three (17.6%) patients, and recessive ATP6V1B1 mutations in two (11.8%) patients. Compared to other patients, patients with SLC4A1 mutations showed an older age of onset (3.7 ± 2.6 years) and less severe metabolic acidosis at initial presentation. All patients developed nephrocalcinosis, and sensorineural hearing loss was observed in two patients with ATP6V1B1 mutations. Three (17.6%) patients had decreased renal function (chronic kidney disease stage 2), and five (29.4%) patients had persistent growth retardation at the last follow-up. Long-term prognosis showed no genotype–phenotype correlation. Conclusions: SLC4A1 is the most common defective gene in Korean children with dRTA. Patients with SLC4A1 mutations show later onset and milder disease severity. Long-term follow-up of hearing ability, renal function, and growth is necessary for patients with dRTA.
Databáze: OpenAIRE
Externí odkaz: