title: Two novel AGXT mutations identified in primary hyperoxaluria type-1 and distinct morphological and structural difference in kidney stones.
abstract: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease characterized by excessive oxalate accumulation in plasma and urine, resulting in various phenotypes because of allelic and clinical heterogeneity. This study aimed to detect disease-associated genetic mutations in three PH1 patients in a Chinese family. All AGXT exons and 3 common polymorphisms which might synergistically interact with mutations, including P11L, I340 M and IVSI+74 bp were analyzed by direct sequencing in all family members. It demonstrated that in each of three patients, a previously reported nonsense mutation p.R333(*) was in cis with a novel missense mutation p.M49L in the minor allele characterized by the polymorphism of 74-bp duplication in intron 1, while the other novel missense mutation p.N72I was in trans with both p.R333(*) and P.M49L in the major allele. Kidney stones from two sibling patients were also observed though stereomicroscopic examination and scanning electron microscopy. Distinct morphological and inner-structure differences in calculi were noticed, suggesting clinical heterozygosity of PH1 to a certain extent. In brief, two novel missense mutations were identified probably in association with PH1, a finding which should provide an accurate tool for prenatal diagnosis, genetic counseling and screening for potential presymptomatic individuals.
authors.affiliation: Department of Nephrology, the Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.|Central Laboratory, the Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266003, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Nephrology, the Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.|Central Laboratory, the Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266003, China.
authors.forename: Jingru
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Nephrology, the Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Lang
authors.affiliation: Department of Nephrology, the Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.|Central Laboratory, the Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266003, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Nephrology, the Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.|Central Laboratory, the Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266003, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Wang
authors.affiliation: Central Laboratory, the Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266003, China.
authors.forename: Xiangzhong
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Nephrology, the Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.|Central Laboratory, the Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266003, China.
authors.forename: Leping
authors.initials: L
authors.lastname: Shao
mesh_terms: D000328:Adult; D000483:Alleles; D015897:Comorbidity; D004252:DNA Mutational Analysis; D017809:Fatal Outcome; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006960:Hyperoxaluria, Primary / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D007669:Kidney Calculi / Q000000981:diagnostic imaging / Q000473:pathology*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D014057:Tomography, X-Ray Computed; D000637:Transaminases / Q000235:genetics*
chemical_list: D000637:Transaminases; C019635:Alanine-glyoxylate transaminase