Novel homozygous OSGEP gene pathogenic variants in two unrelated patients with Galloway-Mowat syndrome: case report and review of the literature
Por:
Domingo-Gallego, A, Furlano, M, Pybus, M, Barraca, D, Martinez, AB, Munoz, EM, Torra, R, Ars, E
Publicada:
11 abr 2019
Resumen:
Background: 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.
Case presentation: 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.
Conclusions; 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.
Filiaciones:
Domingo-Gallego, A:
Univ Autonoma Barcelona, Inst Invest Carlos 3, Fundacio Puigvert, Mol Biol Lab,REDinREN,IIB St Pau, Cartagena 340-350, Barcelona 08025, Catalonia, Spain
Univ Autonoma Barcelona, Inst Invest Carlos 3, Fundacio Puigvert, Nephrol Dept,REDinREN,IIB St Pau, Barcelona, Catalonia, Spain
Furlano, M:
Univ Autonoma Barcelona, Inst Invest Carlos 3, Fundacio Puigvert, Nephrol Dept,REDinREN,IIB St Pau, Barcelona, Catalonia, Spain
Pybus, M:
Univ Autonoma Barcelona, Inst Invest Carlos 3, Fundacio Puigvert, Mol Biol Lab,REDinREN,IIB St Pau, Cartagena 340-350, Barcelona 08025, Catalonia, Spain
Univ Autonoma Barcelona, Inst Invest Carlos 3, Fundacio Puigvert, Nephrol Dept,REDinREN,IIB St Pau, Barcelona, Catalonia, Spain
Barraca, D:
Hosp Gen Univ Gregorio Maranon, Madrid, Spain
Martinez, AB:
Hosp Gen Univ Gregorio Maranon, Madrid, Spain
Munoz, EM:
Hosp Univ Mutua Terrassa, Barcelona, Catalonia, Spain
Torra, R:
Univ Autonoma Barcelona, Inst Invest Carlos 3, Fundacio Puigvert, Nephrol Dept,REDinREN,IIB St Pau, Barcelona, Catalonia, Spain
Ars, E:
Univ Autonoma Barcelona, Inst Invest Carlos 3, Fundacio Puigvert, Nephrol Dept,REDinREN,IIB St Pau, Barcelona, Catalonia, Spain
Univ Autonoma Barcelona, Inst Invest Carlos 3, Fundacio Puigvert, Mol Biol Lab,REDinREN,IIB St Pau, Cartagena 340-350, Barcelona 08025, Catalonia, Spain
Gold, Green Published
|