ClinGen Dosage Sensitivity Curation Page

PAX2

  • Curation Status: Complete

Location Information

  • 10q24.31
  • GRCh37/hg19 chr10: 102,495,466-102,589,698
  • View: NCBI | Ensembl | UCSC
  • GRCh38/hg38 chr10: 100,732,940-100,829,941
  • View: NCBI | Ensembl | UCSC
Select assembly: (NC_000010.10) (NC_000010.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
21285886 Raca et al. (2011) reported a 240 kb deletion encompassing the entire PAX2 coding region and a portion of the FAM178A (C20orf6) gene in a patient with renal-coloboma syndrome. This deletion was identified through array CGH. Follow-up testing with proband's parents were not performed.
11241473 Ford et al. (2001) reported a frameshift variant in exon 2 of the PAX2 gene (c.619insG; NM_003990.3 c.76dup; p.Val26Glyfs*28) in a family with renal-coloboma syndrome through targeted Sanger sequencing of the PAX2 gene. The frameshift variant was first identified in a proband (IV-7, Fig. 1) who presented prenatally with renal disease. Three affected family members spanning 3 generations from the proband (II-3, III-19, III-20, Fig. 1) were identified to have the c.619insC variant. Three non-affected family members (II-5, III-8, III-8, Fig. 1) were identified to not have the c.619insC variant.
22213154 Bower et al. (2012) within their review report 3 unrelated probands with renal-coloboma syndrome with de novo frameshift variants in PAX2 (Family 66, 73, 75; Supp Table S1) . Two unrelated probands with renal-coloboma syndrome with frameshift variants in PAX2 were reported in which one parent was affected and shared the same frameshift variant (Family 43, 68; Supp Table S1). Two unrelated probands with renal-coloboma were found to have frameshift variants in PAX2 (Family 62, 70; Supp Table 1), however follow-up testing with proband?s parents were not performed. Within the review by Bower et al. the authors reference additional studies of probands with renal-coloboma syndrome with either frameshift variants (15 reports) or nonsense variants (9 reports).

Haploinsufficiency phenotype comments:

PMID: 11730657 Chung et al. (2001) reported a de novo frameshift variant in exon 2 of the PAX2 gene (c.602delT; NM_003990.3 c.59del; p.Val20Glyfs*9) in a 9 year old female with autosomal dominant renal-coloboma (bilateral optic nerve coloboma or dysplasia and renal hypoplasia) through targeted Sanger sequencing. Patient?s mother and father demonstrated normal sequence through Sanger and ASO methods. PMID: 21108633 Negrisolo et al. (2011) identified a female with a de novo frameshift variant in the PAX2 gene (NM_003987 c.69delC, p.Val26Cysfs*3) presenting with end?stage renal disease secondary to bilateral reflux nephropathy and renal hypodysplasia. Ophthalmologic examination showed myopia and isotropy of the right eye. The patient also had mild bilateral sensorineural hearing loss. PMID: 17403695 Benetti et al. (2007) reported a 5 month old female with renal hypoplasia without optic coloboma who had a 7.9 Mb deletion observed by array CGH. This deletion encompasses approximately 90 genes, one of which is PAX2. Loss of PAX2 was confirmed by RT-PCR. Furthermore, chromosome analysis demonstrated a deletion of chromosome 10: 46,XX,del(10)(q23.2q24.3). PMID: 9132492 Narahara et al. (1997) reported a 5 year old male with a de novo t(10;13)(q24.2 or q25.2; q12.3 or q14.1) who presented with optic nerve coloboma-renal disease. Follow-up FISH analysis confirmed the 10q translocation breakpoint occurred within the PAX2 gene.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity