Novel homozygous OSGEP gene pathogenic variants in two unrelated patients with Galloway-Mowat syndrome : case report and review of the literature
Domingo, Andrea (Institut d'Investigació Biomèdica Sant Pau)
Furlano, Monica (Institut d'Investigació Biomèdica Sant Pau)
Pybus, Marc (Institut d'Investigació Biomèdica Sant Pau)
Barraca, Daniel (Hospital General Universitario Gregorio Marañón)
Martínez, Ana Belén (Hospital General Universitario Gregorio Marañón)
Mora Muñoz, Emiliano (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Torra Balcells, Roser (Institut d'Investigació Biomèdica Sant Pau)
Ars, Elisabet (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Date:	2019
Abstract:	Galloway-Mowat syndrome (GAMOS) is a rare autosomal recessive disorder characterized by early-onset nephrotic syndrome and microcephaly with brain anomalies. WDR73 pathogenic variants were described as the first genetic cause of GAMOS and, very recently, four novel causative genes, OSGEP, LAGE3, TP53RK, and TPRKB, have been identified. We present the clinical and genetic characteristics of two unrelated infants with clinical suspicion of GAMOS who were born from consanguineous parents. Both patients showed a similar clinical presentation, with early-onset nephrotic syndrome, microcephaly, brain atrophy, developmental delay, axial hypotonia, and early fatality. We identified two novel likely disease-causing variants in the OSGEP gene. These two cases, in conjunction with the findings of a literature review, indicate that OSGEP pathogenic variants are associated with an earlier onset of nephrotic syndrome and shorter life expectancy than WDR73 pathogenic variants. Our findings expand the spectrum of pathogenic variants in the OSGEP gene and, taken in conjunction with the results of the literature review, suggest that the OSGEP gene should be considered the main known monogenic cause of GAMOS. Early genetic diagnosis of GAMOS is of paramount importance for genetic counseling and family planning.
Grants:	Instituto de Salud Carlos III PI16-01998 Instituto de Salud Carlos III PI18-00362 Instituto de Salud Carlos III RD16-0009-0019
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Galloway-Mowat syndrome ; Nephrotic syndrome ; OSGEP ; KEOPS complex ; Genetic testing ; Case report
Published in:	BMC Nephrology, Vol. 20 (april 2019) , ISSN 1471-2369

DOI: 10.1186/s12882-019-1317-y
PMID: 30975089

8 p, 1.5 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles