PMID- 36835576
OWN - NLM
STAT- MEDLINE
DCOM- 20230228
LR  - 20230301
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 4
DP  - 2023 Feb 19
TI  - PAX2 and CAKUT Phenotypes: Report on Two New Variants and a Review of Mutations 
      from the Leiden Open Variation Database.
LID - 10.3390/ijms24044165 [doi]
LID - 4165
AB  - PAX2 is a transcription factor expressed during embryogenesis in the eye, ear, 
      CNS, and genitourinary tract, and is one of the major regulators of kidney 
      development. Mutations in this gene are associated with papillorenal syndrome 
      (PAPRS), a genetic condition characterized by optic nerve dysplasia and renal 
      hypo/dysplasia. In the last 28 years, many cohort studies and case reports 
      highlighted PAX2's involvement in a large spectrum of kidney malformations and 
      diseases, with or without eye abnormalities, defining the phenotypes associated 
      with PAX2 variants as "PAX2-related disorders". Here, we reported two new 
      sequence variations and reviewed PAX2 mutations annotated on the Leiden Open 
      Variation Database 3.0. DNA was extracted from the peripheral blood of 53 
      pediatric patients with congenital abnormalities of the kidney and urinary tract 
      (CAKUT). PAX2 gene-coding exonic and flanking intronic regions were sequenced 
      with Sanger technology. Two unrelated patients and two twins carrying one known 
      and two unknown PAX2 variations were observed. The frequency of PAX2-related 
      disorders in this cohort was 5.8%, considering all CAKUT phenotypes (16.7% in the 
      PAPRS phenotype and 2.5% in non-syndromic CAKUT). Although PAX2 mutations have a 
      higher frequency in patients with PAPRS or non-syndromic renal hypoplasia, from 
      the review of variants reported to date in LOVD3, PAX2-related disorders are 
      detected in pediatric patients with other CAKUT phenotypes. In our study, only 
      one patient had a CAKUT without an ocular phenotype, but his twin had both renal 
      and ocular involvement, confirming the extreme inter- and intrafamilial 
      phenotypic variability.
FAU - Negrisolo, Susanna
AU  - Negrisolo S
AUID- ORCID: 0000-0002-2229-1502
AD  - Laboratory of Immunopathology and Molecular Biology of the Kidney, Department of 
      Women's and Children's Health, University of Padova, 35127 Padua, Italy.
AD  - Pediatric Research Institute "IRP Citta della Speranza", 35127 Padua, Italy.
FAU - Benetti, Elisa
AU  - Benetti E
AUID- ORCID: 0000-0002-8939-6376
AD  - Laboratory of Immunopathology and Molecular Biology of the Kidney, Department of 
      Women's and Children's Health, University of Padova, 35127 Padua, Italy.
AD  - Pediatric Research Institute "IRP Citta della Speranza", 35127 Padua, Italy.
AD  - Pediatric Nephrology, Department of Women's and Children's Health, Padua 
      University Hospital, 35128 Padua, Italy.
LA  - eng
GR  - ND/Il Sogno di Stefano Charity/
PT  - Journal Article
DEP - 20230219
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (PAX2 protein, human)
RN  - 0 (PAX2 Transcription Factor)
RN  - Allanson Pantzar McLeod syndrome
RN  - Cakut
RN  - Papillorenal syndrome
SB  - IM
MH  - Humans
MH  - Kidney/abnormalities
MH  - *Kidney Diseases/genetics
MH  - Mutation
MH  - *PAX2 Transcription Factor/genetics
MH  - Phenotype
MH  - *Urinary Tract
MH  - *Vesico-Ureteral Reflux/genetics
PMC - PMC9962628
OTO - NOTNLM
OT  - CAKUT
OT  - LOVD
OT  - PAX2 gene
OT  - RHD
OT  - renal hypodysplasia
COIS- The authors declare no conflict of interest.
EDAT- 2023/02/26 06:00
MHDA- 2023/03/03 06:00
PMCR- 2023/02/19
CRDT- 2023/02/25 02:55
PHST- 2022/12/31 00:00 [received]
PHST- 2023/02/13 00:00 [revised]
PHST- 2023/02/15 00:00 [accepted]
PHST- 2023/02/25 02:55 [entrez]
PHST- 2023/02/26 06:00 [pubmed]
PHST- 2023/03/03 06:00 [medline]
PHST- 2023/02/19 00:00 [pmc-release]
AID - ijms24044165 [pii]
AID - ijms-24-04165 [pii]
AID - 10.3390/ijms24044165 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Feb 19;24(4):4165. doi: 10.3390/ijms24044165.