A clinico-genetic study of renal coloboma syndrome in children

Abstract

Renal coloboma syndrome (RCS) is an autosomal dominant disorder caused by PAX2 gene mutations and characterized by renal hypoplasia and optic disc coloboma. The clinical findings were retrospectively reviewed, and all coding regions of the PAX2 gene were sequenced, in six children with RCS. A c.619_620insG mutation was detected in five patients, including two siblings, and a novel p.Arg104X mutation was detected in one patient. All the patients had progressive renal dysfunction and bilateral hypoplastic kidneys without vesicoureteral reflux (VUR), but the rate of progression to end-stage renal disease showed some diversity. The ocular manifestations showed wide variability, ranging from subtle optic disc anomalies to microphthalmia. In one family with two affected siblings, maternal germline mosaicism was suggested by an intragenic microsatellite marker study. In conclusion, there are variable renal and ocular manifestations in RCS without significant phenotype-genotype correlations. VUR is not a cardinal renal manifestation of RCS. The possibility of germline mosaicism should be considered during molecular diagnosis and genetic counseling for PAX2 mutations.

Retinal Abnormalities Characteristic of Inherited Renal Disease

“…The renal abnormalities in renal-coloboma syndrome include vesicoureteric reflux, renal hypoplasia, multicystic or dysplastic kidneys, and renal failure. 30,31 The age at presentation and rate of progression to renal failure vary even within families. Ocular features vary from optic disc pits to large chorioretinal coloboma, and abnormalities are usually asymmetrical.…”

Mutations in PAX2 Associate with Adult-Onset FSGS

“…This same mutation was previously described in PRS. 15 In Silico Structural Analysis Detailed molecular modeling was performed to explore the effects of the identified PAX2 missense mutations. The domain structure of PAX2 can be inferred with high reliability because of its high sequence homology with other PAX family proteins for which crystallographic structures are available.…”

Mutación infrecuente en el síndrome renal-coloboma: a propósito de un caso y revisión

“…Dicho gen se considera una de las dianas de la regulación transcripcional del gen supresor de tumores WT1. 11 La mayoría de las mutaciones patogénicas están localizadas en los exones del 2 al 4. La prevalencia de mutaciones en niños afectos de hipodisplasia renal se sitúa en el 6%.…”

“…14 La mutación del PAX2 más frecuente es la c.77dupG, descrita en más de 20 pacientes. 4 La paciente presentó una mutación, la p.Arg104X, que solo ha sido descrita por Cheong et al, 11 en una ocasión. En ese caso, se trataba de un varón de 1 año con ERC, hipodisplasia de ambos riñones ecográficamente, sin lesiones focales en la gammagrafía renal ni existencia de RVU.…”

“…En nuestro caso, existió RVU bilateral, no descrito en este paciente, pero sí de forma global hasta en el 25% de las mutaciones del PAX2 registradas. 11,15 Actualmente, existen más de 80 casos registrados de SRC con mutaciones PAX2, lo que supone, aproximadamente, la mitad de los casos publicados, por lo que se piensa que deben existir otros mecanismos genéticos implicados. 4 Los individuos con diagnóstico de SRC deben recibir un seguimiento estrecho por parte de todas las especialidades implicadas, así como un correcto asesoramiento genético familiar.…”