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Parental Whole-Exome Sequencing Enables Sialidosis Type II Diagnosis due to an NEU1 Missense Mutation as an Underlying Cause of Nephrotic Syndrome in the Child.

Maroofian, R; Schuele, I; Najafi, M; Bakey, Z; Rad, A; Antony, D; Habibi, H; Schmidts, M (2018) Parental Whole-Exome Sequencing Enables Sialidosis Type II Diagnosis due to an NEU1 Missense Mutation as an Underlying Cause of Nephrotic Syndrome in the Child. Kidney Int Rep, 3 (6). pp. 1454-1463. ISSN 2468-0249 https://doi.org/10.1016/j.ekir.2018.07.015
SGUL Authors: Maroofian, Reza

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Abstract

Introduction: Monogenetic renal diseases, including recessively inherited nephrotic syndromes, represent a significant health burden despite being rare conditions. Precise diagnosis, including identification of the underlying molecular cause, is especially difficult in low-income countries and/or if affected individuals are unavailable for biochemical testing. Whole-exome sequencing (WES) has opened up novel diagnostic perspectives for these settings. However, sometimes the DNA of affected individuals is not suitable for WES due to low amounts or degradation. Methods: We report on the use of parental WES with implementation of specific stepwise variant filtering to identify the underlying molecular cause of the childhood-onset nephrotic syndrome as nephrosialidosis resulting from a mutation in NEU1. Results: Sequencing both parents enabled a nephrosialidosis diagnosis in the deceased child. To date, only 16 other cases of nephrosialidosis have been reported in the literature, with only 1 genetically confirmed case. After we reviewed the clinical information of all reported cases, we found that most patients presented with proteinuria, which started at between 2 and 3 years of age. Renal pathology showed mainly focal segmental glomerulosclerosis (FSGS)with vacuolated cells, and steroid treatment was always unsuccessful. Hepatomegaly was present in nearly all cases, whereas corneal clouding and a cherry red spot on the macula was observed in only approximately 50% of cases. Fourteen of 16 previously reported cases were no longer alive at the time of reporting. Conclusions: Our findings demonstrate the power of parental WES to diagnose rare genetic diseases, such as childhood-onset nephrotic syndrome. We further provide a comprehensive overview of the clinical course of nephrosialidosis and raise awareness of this ultra-rare condition as an underlying cause of FSGS.

Item Type: Article
Additional Information: © 2018 International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: NEU1, nephrotic syndrome, sialidosis, whole-exome sequencing
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: Kidney Int Rep
ISSN: 2468-0249
Language: eng
Dates:
DateEvent
November 2018Published
29 July 2018Published Online
23 July 2018Accepted
Publisher License: Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0
Projects:
Project IDFunderFunder ID
DFG CRC1140 KIDGEMDeutsche Forschungsgemeinschafthttp://dx.doi.org/10.13039/501100001659
716344European Research Councilhttp://dx.doi.org/10.13039/501100000781
PubMed ID: 30450471
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/110409
Publisher's version: https://doi.org/10.1016/j.ekir.2018.07.015

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