Genetic stratification reveals COL4A variants and spontaneous remission in Egyptian children with proteinuria in the first 2 years of life
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Genetic stratification reveals COL4A variants and spontaneous remission in Egyptian children with proteinuria in the first 2 years of life. / Elshafey, Samar Atef; Thabet, Mohamed Alaa Eldin Hassan; Abo Elwafa, Reham Abdel Haleem; Schneider, Ronen; Shril, Shirlee; Buerger, Florian; Hildebrandt, Friedhelm; Fathy, Hanan M.
in: ACTA PAEDIATR, Jahrgang 112, Nr. 6, 06.2023, S. 1324-1332.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Genetic stratification reveals COL4A variants and spontaneous remission in Egyptian children with proteinuria in the first 2 years of life
AU - Elshafey, Samar Atef
AU - Thabet, Mohamed Alaa Eldin Hassan
AU - Abo Elwafa, Reham Abdel Haleem
AU - Schneider, Ronen
AU - Shril, Shirlee
AU - Buerger, Florian
AU - Hildebrandt, Friedhelm
AU - Fathy, Hanan M
N1 - © 2023 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.
PY - 2023/6
Y1 - 2023/6
N2 - AIM: The earlier the onset of proteinuria, the higher the incidence of genetic forms. Therefore, we aimed to analyse the spectrum of monogenic proteinuria in Egyptian children presenting at age <2 years.METHODS: The results of 27-gene panel or whole-exome sequencing were correlated with phenotype and treatment outcomes in 54 patients from 45 families.RESULTS: Disease-causing variants were identified in 29/45 (64.4%) families. Mutations often occurred in three podocytopathy genes: NPHS1, NPHS2 and PLCE1 (19 families). Some showed extrarenal manifestations. Additionally, mutations were detected in 10 other genes, including novel variants of OSGEP, SGPL1 and SYNPO2. COL4A variants phenocopied isolated steroid-resistant nephrotic syndrome (2/29 families, 6.9%). NPHS2 M1L was the single most common genetic finding beyond the age of 3 months (4/18 families, 22.2%). Biopsy results did not correlate with genotypes (n = 30). On renin-angiotensin-aldosterone system antagonists alone, partial and complete remission occurred in 3/24 (12.5%) patients with monogenic proteinuria each, whereas 6.3% (1/16) achieved complete remission on immunosuppression.CONCLUSION: Genotyping is mandatory to avoid biopsies and immunosuppression when proteinuria presents at age <2 years. Even with such a presentation, COL4A genes should be included. NPHS2 M1L was prevalent in Egyptian children (4 months-2 years) with proteinuria, demonstrating precision diagnostic utility.
AB - AIM: The earlier the onset of proteinuria, the higher the incidence of genetic forms. Therefore, we aimed to analyse the spectrum of monogenic proteinuria in Egyptian children presenting at age <2 years.METHODS: The results of 27-gene panel or whole-exome sequencing were correlated with phenotype and treatment outcomes in 54 patients from 45 families.RESULTS: Disease-causing variants were identified in 29/45 (64.4%) families. Mutations often occurred in three podocytopathy genes: NPHS1, NPHS2 and PLCE1 (19 families). Some showed extrarenal manifestations. Additionally, mutations were detected in 10 other genes, including novel variants of OSGEP, SGPL1 and SYNPO2. COL4A variants phenocopied isolated steroid-resistant nephrotic syndrome (2/29 families, 6.9%). NPHS2 M1L was the single most common genetic finding beyond the age of 3 months (4/18 families, 22.2%). Biopsy results did not correlate with genotypes (n = 30). On renin-angiotensin-aldosterone system antagonists alone, partial and complete remission occurred in 3/24 (12.5%) patients with monogenic proteinuria each, whereas 6.3% (1/16) achieved complete remission on immunosuppression.CONCLUSION: Genotyping is mandatory to avoid biopsies and immunosuppression when proteinuria presents at age <2 years. Even with such a presentation, COL4A genes should be included. NPHS2 M1L was prevalent in Egyptian children (4 months-2 years) with proteinuria, demonstrating precision diagnostic utility.
KW - Humans
KW - Remission, Spontaneous
KW - Egypt
KW - Intracellular Signaling Peptides and Proteins/genetics
KW - Membrane Proteins/genetics
KW - Nephrotic Syndrome/therapy
KW - Proteinuria/genetics
KW - Mutation
U2 - 10.1111/apa.16732
DO - 10.1111/apa.16732
M3 - SCORING: Journal article
C2 - 36847718
VL - 112
SP - 1324
EP - 1332
JO - ACTA PAEDIATR
JF - ACTA PAEDIATR
SN - 0803-5253
IS - 6
ER -