title: Genotype and Phenotype Analysis in Pediatric Patients with Cystinuria.
abstract: Cystinuria is an inherited disorder characterized by defective renal reabsorption of cystine and dibasic amino acids leading to nephrolithiasis. This study was conducted to analyze the genotypes and phenotypes of pediatric patients with cystinuria. Eight children from Seoul National University Hospital and Asan Medical Center presenting with cystinuria from January 2003 to June 2016 were retrospectively analyzed. Mutational studies were performed by direct sequencing. Two of the 8 were male and 6 were female. The median ages at onset and diagnosis were 1.5 (range, 0.3-13.6) and 2.6 (range, 0.7-16.7) years, respectively. The median followed up was 7.7 (range, 3.4-14.0) years. Mutational analyses were performed in 7 patients and revealed biallelic SLC3A1 mutations (AA genotype) in 4 patients, a single heterozygous SLC3A1 mutation (A- genotype) in 1 patient, biallelic SLC7A9 mutations (BB genotype) in 1 patient, and a single heterozygous SLC7A9 mutation (B- genotype) in 1 patient. Two of the mutations were novel. No genotype-phenotype correlations were observed, except for earlier onset age in patients with non-AA genotypes than in patients with the AA genotype. All patients suffered from recurrent attacks of symptomatic nephrolithiasis, which lead to urologic interventions. At the last follow-up, 3 patients had a mild-to-moderate degree of renal dysfunction. This is the first study of genotypic and phenotypic analyses of patients with cystinuria in Korea.
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Ji Hyun
authors.identifier: http://orcid.org/0000-0002-3051-1691
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Eujin
authors.identifier: http://orcid.org/0000-0002-4413-468X
authors.initials: E
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Hye Sun
authors.identifier: http://orcid.org/0000-0001-8525-1471
authors.initials: HS
authors.lastname: Hyun
authors.affiliation: Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center Children's Hospital, Seoul, Korea.
authors.forename: Beom Hee
authors.identifier: http://orcid.org/0000-0001-9709-2631
authors.initials: BH
authors.lastname: Lee
authors.affiliation: Medical Genetics Center, University of Ulsan College of Medicine, Asan Medical Center Children's Hospital, Seoul, Korea.
authors.forename: Gu Hwan
authors.identifier: http://orcid.org/0000-0002-7056-7446
authors.initials: GH
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center Children's Hospital, Seoul, Korea.
authors.forename: Joo Hoon
authors.identifier: http://orcid.org/0000-0001-8010-3605
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center Children's Hospital, Seoul, Korea.
authors.forename: Young Seo
authors.identifier: http://orcid.org/0000-0001-7653-2036
authors.initials: YS
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.|Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, Korea.
authors.forename: Hee Gyung
authors.identifier: http://orcid.org/0000-0001-8323-5320
authors.initials: HG
authors.lastname: Kang
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.|Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Il Soo
authors.identifier: http://orcid.org/0000-0001-5428-6209
authors.initials: IS
authors.lastname: Ha
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.|Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, Korea.|Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea. cheonghi@snu.ac.kr.
authors.forename: Hae Il
authors.identifier: http://orcid.org/0000-0001-7556-1265
authors.initials: HI
authors.lastname: Cheong
mesh_terms: D000293:Adolescent; D026923:Amino Acid Transport Systems, Basic / Q000235:genetics; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003555:Cystinuria / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D053040:Nephrolithiasis / Q000209:etiology; D011110:Polymorphism, Genetic; D056910:Republic of Korea; D012189:Retrospective Studies; D017693:Sodium Bicarbonate / Q000627:therapeutic use; D008625:Tiopronin / Q000627:therapeutic use
chemical_list: D026923:Amino Acid Transport Systems, Basic; D026921:Amino Acid Transport Systems, Neutral; C489857:SLC3A1 protein, human; D017693:Sodium Bicarbonate; D004247:DNA; D008625:Tiopronin
keywords: Cystinuria; Gene mutation; Genotype; Phenotype; SLC3A1 Gene; SLC7A9 Gene