Early presentation of cystic kidneys in a family with a homozygous INVS mutation.
Am J Med Genet A
; 164A(7): 1627-34, 2014 Jul.
Article
en En
| MEDLINE
| ID: mdl-24677454
ABSTRACT
Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease that is the most frequent monogenic cause of end-stage renal disease in children. Infantile NPHP, often in combination with other features like situs inversus, are commonly caused by mutations in the INVS gene. INVS encodes the ciliary protein inversin, and mutations induce dysfunction of the primary cilia. In this article, we present a family with two severely affected fetuses that were aborted after discovery of grossly enlarged cystic kidneys by ultrasonography before 22 weeks gestation. Exome sequencing showed that the fetuses were homozygous for a previously unreported nonsense mutation, resulting in a truncation in the IQ1 domain of inversin. This mutation induces nonsense-mediated RNA decay, as suggested by a reduced RNA level in fibroblasts derived from the fetus. However, a significant amount of mutant INVS RNA was present in these fibroblasts, yielding mutant inversin protein that was mislocalized. In control fibroblasts, inversin was present in the ciliary axoneme as well as at the basal body, whereas in the fibroblasts from the fetus, inversin could only be detected at the basal body. The phenotype of both fetuses is partly characteristic of infantile NPHP and Potter sequence. We also identified that the fetuses had mild skeletal abnormalities, including shortening and bowing of long bones, which may expand the phenotypic spectrum associated with INVS mutations.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
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Enfermedades Renales Quísticas
/
Homocigoto
/
Mutación
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Female
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Humans
Idioma:
En
Revista:
Am J Med Genet A
Asunto de la revista:
GENETICA MEDICA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Países Bajos