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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Identification of 99 novel mutations in a worldwide cohort of 1,056 patients with a nephronophthisis-related ciliopathy
Human Genetics, Volume 132, No. 8, Year 2013
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Description
Nephronophthisis-related ciliopathies (NPHP-RC) are autosomal-recessive cystic kidney diseases. More than 13 genes are implicated in its pathogenesis to date, accounting for only 40 % of all cases. High-throughput mutation screenings of large patient cohorts represent a powerful tool for diagnostics and identification of novel NPHP genes. We here performed a new high-throughput mutation analysis method to study 13 established NPHP genes (NPHP1-NPHP13) in a worldwide cohort of 1,056 patients diagnosed with NPHP-RC. We first applied multiplexed PCR-based amplification using Fluidigm Access-Array™ technology followed by barcoding and next-generation resequencing on an Illumina platform. As a result, we established the molecular diagnosis in 127/1,056 independent individuals (12.0 %) and identified a single heterozygous truncating mutation in an additional 31 individuals (2.9 %). Altogether, we detected 159 different mutations in 11 out of 13 different NPHP genes, 99 of which were novel. Phenotypically most remarkable were two patients with truncating mutations in INVS/NPHP2 who did not present as infants and did not exhibit extrarenal manifestations. In addition, we present the first case of Caroli disease due to mutations in WDR19/NPHP13 and the second case ever with a recessive mutation in GLIS2/NPHP7. This study represents the most comprehensive mutation analysis in NPHP-RC patients, identifying the largest number of novel mutations in a single study worldwide. © 2013 Springer-Verlag Berlin Heidelberg.
Authors & Co-Authors
Halbritter, J.
United States, Ann Arbor
Michigan Medicine
Porath, Jonathan D.
United States, Ann Arbor
Michigan Medicine
Diaz, Katrina A.
United States, Ann Arbor
Michigan Medicine
Braun, Daniela Anne
United States, Ann Arbor
Michigan Medicine
Kohl, Stefan
United States, Ann Arbor
Michigan Medicine
Chaki, Moumita
United States, Ann Arbor
Michigan Medicine
Allen, Susan J.
United States, Ann Arbor
Michigan Medicine
Soliman Elshakhs, Neveen A.
Egypt, Giza
Cairo University
Egypt, Cairo
Egyptian Group for Orphan Renal Diseases Egord
Hildebrandt, Friedhelm
United States, Ann Arbor
Michigan Medicine
United States, Chevy Chase
Howard Hughes Medical Institute
Otto, Edgar A.
United States, Ann Arbor
Michigan Medicine
Statistics
Citations: 10
Authors: 10
Affiliations: 4
Identifiers
Doi:
10.1007/s00439-013-1297-0
ISSN:
03406717
e-ISSN:
14321203
Research Areas
Cancer
Genetics And Genomics
Health System And Policy
Study Design
Cohort Study