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Typical renal-coloboma syndrome phenotype in a patient with a submicroscopic deletion of the PAX2 gene.

ABSTRACT: We present a patient with optic nerve hypoplasia, secondary strabismus, mild deafness, abnormal external ear helices, and renal hypoplasia. The clinical phenotype was consistent with renal-coloboma syndrome, but no point mutation in the PAX2 gene could be identified. High-resolution array comparative genomic hybridization (aCGH) analysis showed that this patient has a submicroscopic deletion on chromosome 10, affecting the entire coding region of the PAX2 gene. This finding provided the molecular confirmation of the patient's clinical diagnosis and showed that, in addition to point mutations, deletions of the PAX2 gene contribute to the etiology of the renal-coloboma syndrome.

SUBMITTER: Laimutis K

PROVIDER: S-EPMC4098919 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Typical renal-coloboma syndrome phenotype in a patient with a submicroscopic deletion of the PAX2 gene.

Laimutis Kucinskas K Jackson Craig C Xu Xinjie X Warman Berta B Sarunas Rudaitis R Andriuskeviciute Irena I Birute Pundziene P Schimmenti Lisa A LA Raca Gordana G

American journal of medical genetics. Part A 20120511 6

We present a patient with optic nerve hypoplasia, secondary strabismus, mild deafness, abnormal external ear helices, and renal hypoplasia. The clinical phenotype was consistent with renal-coloboma syndrome, but no point mutation in the PAX2 gene could be identified. High-resolution array comparative genomic hybridization (aCGH) analysis showed that this patient has a submicroscopic deletion on chromosome 10, affecting the entire coding region of the PAX2 gene. This finding provided the molecula ...[more]

PMID: 22581475

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Further delineation of renal-coloboma syndrome in patients with extreme variability of phenotype and identical PAX2 mutations.

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A novel truncating PAX2 mutation in a boy with renal coloboma syndrome with focal segmental glomerulosclerosis causing rapid progression to end-stage kidney disease.

Project description:Renal coloboma syndrome (RCS, MIM#120330), also known as papillorenal syndrome, is an inherited autosomal dominant disease characterized by ocular and/or renal involvement due to PAX2 mutation. The renal involvement typically consists of a hypo/dysplatic kidney and/or vesicoureteral reflux. Recent studies reported that missense PAX2 mutations cause familial focal segmental glomerular sclerosis (FSGS) without renal morphological malformations. To date, the reports of genotype-phenotype correlation including pathological findings regarding PAX2 mutations are scarce. We report a case of RCS with a novel PAX2 mutation that was pathologically diagnosed as FSGS and rapidly progressed to end-stage kidney failure (ESKD) with a review of past literature. A 6-year-old boy, who had bilateral coloboma and loss of vision in the left eye, was noted non-nephrotic proteinuria and renal dysfunction via school urine screening. Abdominal ultrasound showed no renal and urinary tract malformations and kidney biopsy showed FSGS. Genetic analysis revealed a novel insertion-deletion mutation in PAX2 (NM003987.4: c.70_72delinsA; p.Gly24Argfs*29). His kidney function deteriorated gradually during the following 2 years and kidney transplantation was performed at 9 years of age. In previous reports describing PAX2 mutations with FSGS, affected individuals with missense PAX2 mutations developed ESKD in adulthood, whereas one case with truncating PAX2 mutations developed ESKD in childhood similar to the current case. Our case highlighted the association of truncating PAX2 mutations with the risk of rapid progression to ESKD. Thus, PAX2 mutations should be included in genetic screening for such cases even in the absence of renal and urinary tract malformations.

| S-EPMC6990249 | biostudies-literature

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