Homonucleotide expansion and contraction mutations ofPAX2 and inclusion of Chiari 1 malformation as part of Renal-Coloboma syndrome

Schimmenti, Lisa A.; Shim, Heather H.; Wirtschafter, Jonathan D.; Panzarino, Valerie; Kashtan, Clifford E.; Kirkpatrick, Susan J.; Wargowski, David S.; France, Thomas D.; Michel, Eduard; Dobyns, William B.

doi:10.1002/(sici)1098-1004(199911)14:5<369::aid-humu2>3.0.co;2-e

Cited by 48 publications

(31 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[1][2][3][4][5][6][7] So far, eight different PAX2 mutations have been reported in 13 patients with RCS. [7][8][9][10][11][12][13] In all previously reported cases, patients presented with RCS or renal hypoplasia with mild ocular manifestations described as optic disc dysplasia or papillo-renal syndrome. Here, we report on five additional cases of PAX2 mutations in patients with RCS.…”

Section: Discussionmentioning

confidence: 99%

“…7 Since then, eight different PAX2 mutations and a chromosome 10/13 de novo translocation have been identified in 13 unrelated patients. [7][8][9][10][11][12][13][14] It has been shown that PAX2 gene mutations are associated with both inter and intrafamilial phenotypic variability; all patients share renal and ocular abnormalities, while some present with hearing loss, mental retardation or seizures. 9 Several Pax2 mutant mice are known: Pax2 1Neu resulting from a Pax2 frameshift mutation, 15 Krd carrying a large chromosomal deletion encompassing the Pax2 gene (kidney and retinal defect, 16 ), and the Pax2 knock-out mouse.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

PAX2 mutations in renal–coloboma syndrome: mutational hotspot and germline mosaicism

et al. 2000

View full text Add to dashboard Cite

The renal-coloboma syndrome (RCS, MIM 120330) is an autosomal dominant disorder caused by PAX2 gene mutations. We screened the entire coding sequence of the PAX2 gene for mutations in nine patients with RCS. We found five heterozygous PAX2 gene mutations: a dinucleotide insertion (2G) at position 619 in one sporadic RCS case, a single nucleotide insertion (619 + G) in three unrelated cases, and a single nucleotide deletion in a familial case. In this familial case, three affected sibs showed a striking ocular phenotypic variability. Each of the sibs carried a 619insG mutation, whilst unaffected parents did not, suggesting the presence of germline mosaicism. Interestingly, the 619insG mutation has been previously reported in several patients and is also responsible for the Pax2 1Neu mouse mutant, an animal model of human RCS. This study confirms the critical role of the PAX2 gene in human renal and ocular development. In addition, it emphasises the high variability of ocular defects associated with PAX2 mutations ranging from subtle optic disc anomalies to microphthalmia. Finally, the presence of PAX2 germline mosaicism highlights the difficulties associated with genetic counselling for PAX2 mutations. European Journal of Human Genetics (2000) 8, 820-826.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

PAX2 mutations in renal–coloboma syndrome: mutational hotspot and germline mosaicism

et al. 2000

View full text Add to dashboard Cite

show abstract

“…Renal and/or ocular anomalies are found in all patients, but the type and the severity of these abnormalities can vary markedly. Commonly observed manifestations that affect the kidneys include renal hypoplasia and vesicoureteric reflux (VUR), both of which can lead to renal insufficiency (1)(2)(3)(4)(5)(6)(7)(8)(9). Extrarenal manifestations can include sensorineural hearing loss, Arnold Chiari malformation, seizures of unknown cause, and joint laxity, but these are reported in Ͻ20% of patients (1,5,7,10).…”

mentioning

confidence: 99%

“…All mutations (Table 1) are recorded in the human PAX2 allelic variant database (http://pax2.hgu.mrc.ac.uk/) and include nucleotide substitutions (4,6,20,21), insertions (1,6,7,9,10), and deletions (1,5,7,10,(22)(23)(24), with a single reported case of a de novo translocation (3,10,13). Although variability is found with differing mutations, there is also phenotypic variability with the same mutation and within the same family.…”

mentioning

confidence: 99%

Multicystic Dysplastic Kidney and Variable Phenotype in a Family with a Novel Deletion Mutation of PAX2

Fletcher

Berman³

et al. 2005

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

The renal coloboma syndrome (OMIM 120330) is caused by mutations in the PAX2 gene. Typical findings in these patients include renal hypoplasia, renal insufficiency, vesicoureteric reflux, and optic disc coloboma. A family with a novel heterozygous 10-bp deletion in exon 2 of the PAX2 gene leading to a truncating mutation and variable phenotype across three generations is reported. The first presentation of multicystic dysplastic kidney in this syndrome is reported. The possibility that abnormal PAX2 protein in this case may cause a dominant negative effect also is discussed. The finding of multicystic dysplastic kidney in renal coloboma syndrome could suggest that PAX2 may play a role in early ureteric obstruction and subsequent renal maldevelopment.

show abstract

“…2 Patients with a heterozygous PAX2 mutation ultimately develop end-stage renal disease requiring dialysis or transplant. 3 Some patients with renal coloboma syndrome have to undergo a renal transplant, 3,4 but there are no reported cases of an ABO-incompatible living-donor renal transplant. To our knowledge, this is the first report of an ABO-incompatible living-donor renal transplant without splenectomy performed in a patient with renal coloboma syndrome.…”

Section: Introductionmentioning

confidence: 99%

Untitled

Kobayashi

Hayashi²,

Ishii³

et al. 2014

Exp Clin Transplant

View full text Add to dashboard Cite

To our knowledge, this is the first report of an ABO-incompatible living-donor renal transplant without a splenectomy performed in a patient with renal coloboma syndrome, a rare disorder caused by PAX2 gene mutations, and that presents with renal and optic nerve hypodysplasia and disorders of the central nervous system. Many patients with renal coloboma syndrome develop end-stage renal disease requiring renal replacement therapy. Few reports of a well-defined course of renal transplant for coloboma syndrome have been published. We treated a 22-year-old man who had end-stage renal disease from renal coloboma syndrome. We performed an ABO-incompatible living-donor renal transplant with a kidney donated by his father. Two years after the transplant, the patient has good preserved renal function, and his compliance with the immunosuppressive regimen was good.

show abstract

Homonucleotide expansion and contraction mutations ofPAX2 and inclusion of Chiari 1 malformation as part of Renal-Coloboma syndrome

Cited by 48 publications

References 22 publications

PAX2 mutations in renal–coloboma syndrome: mutational hotspot and germline mosaicism

PAX2 mutations in renal–coloboma syndrome: mutational hotspot and germline mosaicism

Multicystic Dysplastic Kidney and Variable Phenotype in a Family with a Novel Deletion Mutation of PAX2

Untitled

Contact Info

Product

Resources

About