<i>PAX2</i> mutations in fetal renal hypodysplasia

Martinovic-Bouriel, Jelena; Benachi, Alexandra; Bonnière, Maryse; Brahimi, N.; Esculpavit, Chantal; Morichon, Nicole; Vekemans, Michel; Antignac, Corinne; Salomon, Rémi; Encha‐Razavi, Férechté; Attié‐Bitach, Tania; Gubler, Marie–Claire

doi:10.1002/ajmg.a.33133

Cited by 34 publications

(30 citation statements)

References 25 publications

(35 reference statements)

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“…These genes were chosen, because (1) they are routinely screened in our laboratory, (2) they have been shown to also be involved in patients with CAKUT without extrarenal anomalies (5,(13)(14)(15), and (3) PAX2 was recently shown to be involved in one case of severe prenatal CAKUT (17). Thirty-one fetuses had been previously screened for RET mutations in another study (11).…”

Section: Discussionmentioning

confidence: 99%

Severe Prenatal Renal Anomalies Associated with Mutations in HNF1B or PAX2 Genes

Madariaga¹,

Morinière²,

Jeanpierre³

et al. 2013

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Congenital anomalies of the kidney and urinary tract (CAKUT) are a frequent cause of renal failure in children, and their detection in utero is now common with fetal screening ultrasonography. The clinical course of CAKUT detected before birth is very heterogeneous and depends on the level of nephron reduction. The most severe forms cause life-threatening renal failure, leading to perinatal death or the need for very early renal replacement therapy.Design, setting, participants, & measurements This study reports the screening of two genes (HNF1B and PAX2) involved in monogenic syndromic CAKUT in a cohort of 103 fetuses from 91 families with very severe CAKUT that appeared isolated by fetal ultrasound examination and led to termination of pregnancy.Results This study identified a disease-causing mutation in HNF1B in 12 cases from 11 families and a mutation in PAX2 in 4 unrelated cases. Various renal phenotypes were observed, but no case of bilateral agenesis was associated with HNF1B or PAX2 mutations. Autopsy identified extrarenal abnormalities not detected by ultrasonography in eight cases but confirmed the absence of extrarenal defects in eight other cases. A positive family history of renal disease was not significantly more frequent in cases with an identified mutation. Moreover, in cases with an inherited mutation, there was a great phenotypic variability regarding the severity of the renal disease within a single family. ConclusionsOur results suggest that mutations in genes involved in syndromic CAKUT with Mendelian inheritance are not rare in fetal cases with severe CAKUT appearing isolated at prenatal ultrasound, a finding of clinical importance because of genetic counseling.

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Section: Discussionmentioning

confidence: 99%

Severe Prenatal Renal Anomalies Associated with Mutations in HNF1B or PAX2 Genes

Madariaga¹,

Morinière²,

Jeanpierre³

et al. 2013

Clinical Journal of the American Society of Nephrology

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“…Seven fetuses had severe prenatal renal failure with confirmation of the presence of a PAX2 mutation [Martinovic-Bouriel et al, 2010;Supp. Table S1, Families 31, 55, 71, and 82].…”

Section: Fetal Potter Sequencementioning

confidence: 94%

“…A review of four case series revealed that 13/148 (∼9%) of individuals tested due to a primary diagnosis of renal hypoplasia had mutations in the PAX2 gene [Martinovic-Bouriel et al, 2010;Nishimoto et al, 2001;Salomon et al, 2001;Weber et al, 2006]. Of the 13 mutation-positive individuals, further ophthalmological evaluation revealed optic nerve abnormalities in 10 individuals, while three mutation-positive individuals reportedly had a normal ophthalmological exam.…”

Section: Isolated Renal Hypodysplasiamentioning

confidence: 99%

Update of PAX2 mutations in renal coloboma syndrome and establishment of a locus-specific database

et al. 2012

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Renal coloboma syndrome, also known as papillorenal syndrome is an autosomal-dominant disorder characterized by ocular and renal malformations. Mutations in the paired-box gene, PAX2, have been identified in approximately half of individuals with classic findings of renal hypoplasia/dysplasia and abnormalities of the optic nerve. Prior to 2011, there was no actively maintained locus-specific database (LSDB) cataloguing the extent of genetic variation in the PAX2 gene and phenotypic variation in individuals with renal coloboma syndrome. Review of published cases and the collective diagnostic experience of three laboratories in the United States, France, and New Zealand identified 55 unique mutations in 173 individuals from 86 families. The three clinical laboratories participating in this collaboration contributed 28 novel variations in 68 individuals in 33 families, which represent a 50% increase in the number of variations, patients, and families published in the medical literature. An LSDB was created using the Leiden Open Variation Database platform: www.lovd.nl/PAX2. The most common findings reported in this series were abnormal renal structure or function (92% of individuals), ophthalmological abnormalities (77% of individuals), and hearing loss (7% of individuals). Additional clinical findings and genetic counseling implications are discussed.

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“…ESRD may present prenatally with severely hypoplastic or aplastic kidneys and oligohydramnios resulting in fetal loss. 18,27 ESRD has been identified shortly after birth 3,18 and can occur as late as the seventh decade. 12,18 A single case of a surviving infant with Potter sequence, optic nerve malformations and a PAX2 mutation has been reported.…”

Section: Renal Findingsmentioning

confidence: 99%

Renal coloboma syndrome

Schimmenti

2011

Eur J Hum Genet

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In association withRenal coloboma syndrome Renal coloboma syndrome (RCS), also called papillorenal syndrome, is an autosomal dominant condition characterized by optic nerve dysplasia and renal hypodysplasia. The eye anomalies consist of a wide and sometimes excavated dysplastic optic disc with the emergence of the retinal vessels from the periphery of the disc, frequently called optic nerve coloboma or morning glory anomaly. Associated findings may include a small corneal diameter, retinal coloboma, scleral staphyloma, optic nerve cyst and pigmentary macular dysplasia. The kidney abnormalities consist of small and abnormally formed kidneys known as renal hypodysplasia. Histologically, kidneys exhibit fewer than the normal number of glomeruli and these glomeruli are enlarged, a finding called oligomeganephronia. Consequences of the ocular malformations include decreased visual acuity and retinal detachment. Consequences of the renal hypodysplasia include hypertension, proteinuria and renal insufficiency that frequently progresses to end-stage kidney disease. High frequency hearing loss has been reported. Autosomal dominant mutations in PAX2 can be identified in nearly half of all patients with clinical findings suggestive of RCS, however, the majority of published cases have mutations in PAX2, thus biasing the known information about the phenotype.

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PAX2 mutations in fetal renal hypodysplasia

Cited by 34 publications

References 25 publications

Severe Prenatal Renal Anomalies Associated with Mutations in HNF1B or PAX2 Genes

Severe Prenatal Renal Anomalies Associated with Mutations in HNF1B or PAX2 Genes

Update of PAX2 mutations in renal coloboma syndrome and establishment of a locus-specific database

Renal coloboma syndrome

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