title: PAX2 gene mutation in a family with isolated renal hypoplasia.
abstract: The PAX2 gene encodes a transcription factor that plays a critical role in the development of the urogenital tract, eyes, ears, and central nervous system. Recently, renal hypoplasia was observed to be part of the renal-coloboma syndrome, which is caused by heterozygous mutations of the PAX2 gene. The renal-coloboma syndrome is a rare autosomal dominant syndrome that involves optic nerve colobomas and renal anomalies. For investigation of whether PAX2 mutations occur in patients with isolated renal hypoplasia, patient DNA was analyzed for PAX2 mutations, by using PCR and direct sequencing. The study involved 20 patients with bilateral renal hypoplasia associated with decreased renal function. Heterozygous PAX2 mutations were detected in two patients, i.e., a novel nonsense mutation (C to A transversion at position 1566 in exon 9) in patient 1 and another novel nonsense mutation (C to T transversion at position 1318 in exon 7) in patient 2. The nucleotide changes for patients 1 and 2 directly introduced stop codons, presumably resulting in a message for a truncated PAX2 protein that lacked a partial transactivation domain. An ophthalmologic examination revealed a very mild, asymptomatic coloboma in patient 2, whereas the fundus was normal for patient 1. The mutation cosegregated with the presence of renal hypoplasia in the family of patient 1, appearing de novo in the mother of the patient, which strongly suggests that this mutation was the cause of renal hypoplasia in this family. This study demonstrates for the first time that PAX2 mutations can be responsible for isolated renal hypoplasia.
authors.affiliation: Faculty of Health Science, Kobe University School of Medicine, Kobe, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Nishimoto
authors.affiliation: Department of Pediatrics, Kobe University School of Medicine, Kobe, Japan.
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Iijima
authors.affiliation: Faculty of Health Science, Kobe University School of Medicine, Kobe, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Shirakawa
authors.affiliation: Department of Pediatrics, Takasago Municipal Hospital, Takasago, Japan.
authors.forename: Kousaku
authors.initials: K
authors.lastname: Kitagawa
authors.affiliation: Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Satomura
authors.affiliation: Department of Pediatrics, Kobe University School of Medicine, Kobe, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Department of Pediatrics, Wakayama Medical University, Wakayama, Japan.
authors.forename: Norishige
authors.initials: N
authors.lastname: Yoshikawa
mesh_terms: D001483:Base Sequence / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D007668:Kidney / Q000002:abnormalities* / Q000473:pathology; D008297:Male; D051762:PAX2 Transcription Factor; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D004268:DNA-Binding Proteins; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; D014157:Transcription Factors