{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T09:09:53Z","timestamp":1774343393586,"version":"3.50.1"},"reference-count":16,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Steroid-resistant nephrotic syndrome (SRNS) in childhood frequently reflects monogenic podocytopathies in which immunosuppression is ineffective. Biallelic variants in MYO1E, encoding the class I myosin Myo1E, cause a distinctive form of focal segmental glomerulosclerosis (FSGS) often accompanied by \u201cAlport-like\u201d multilamination of the glomerular basement membrane (GBM). Early recognition has therapeutic and prognostic implications. A previously healthy 4-year-old boy presented with generalized edema and nephrotic-range proteinuria. Glucocorticoids induced no remission; sequential calcineurin inhibition (cyclosporine, then tacrolimus) and a single dose of ofatumumab yielded only transient, partial reductions in proteinuria. A first biopsy elsewhere showed FSGS with nonspecific IgM\/C3 trapping; electron microscopy (EM) was not performed. At age 10, repeat biopsy with EM revealed ~30% segmental foot-process effacement, focal GBM thickening (to 1740 nm), irregular lamina densa multilamination, and lamellar duplications without immune-complex deposits\u2014features highly suggestive of hereditary GBM disease. Targeted sequencing identified compound-heterozygous MYO1E variants segregating in trans: a canonical splice-donor change (c.2785+1G&gt;A) and a frameshift (c.3094_3097del; p.Thr1032Profs*73). Each parent was an unaffected heterozygous carrier; the sibling was negative. Supportive therapy with ramipril was continued. At last follow-up (January 2025), renal function was normal (serum creatinine 0.5 mg\/dL; creatinine clearance 122 mL\/min) with stable sub-nephrotic proteinuria (0.52 g\/day; 16 mg\/m2 per hour) and normotension. This case broadens clinicopathologic recognition of MYO1E-associated nephropathy and highlights the teaching point that Alport-like GBM changes are not pathognomonic for type IV collagen disorders but may signal defects in podocyte cytoskeletal anchoring.<\/jats:p>","DOI":"10.3390\/ijms27062838","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T17:02:43Z","timestamp":1774026163000},"page":"2838","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Steroid-Resistant Focal Segmental Glomerulosclerosis with Alport-like Glomerular Basement Membrane Lesions Due to a MYO1E Mutation: A Pediatric Case Report"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8311-5409","authenticated-orcid":false,"given":"Andrea","family":"Angioi","sequence":"first","affiliation":[{"name":"Nephrology, Dialysis and Transplantation Unit, \u201cGiuseppe Brotzu\u201d Hospital, 09121 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doloretta","family":"Piras","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Transplantation Unit, \u201cGiuseppe Brotzu\u201d Hospital, 09121 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Lepori","sequence":"additional","affiliation":[{"name":"Department of Medical Science and Public Health, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1365-6995","authenticated-orcid":false,"given":"Paola","family":"Bianco","sequence":"additional","affiliation":[{"name":"Division of Pathology, \u201cGiuseppe Brotzu\u201d Hospital, 09121 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Floris","sequence":"additional","affiliation":[{"name":"Department of Medical Science and Public Health, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianfranca","family":"Cabiddu","sequence":"additional","affiliation":[{"name":"Department of Medical Science and Public Health, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3566-1995","authenticated-orcid":false,"given":"Antonella","family":"Barreca","sequence":"additional","affiliation":[{"name":"Pathology Unit, Citt\u00e0 della Salute e della Scienza di Torino University Hospital, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonello","family":"Pani","sequence":"additional","affiliation":[{"name":"Department of Medical Science and Public Health, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s40620-016-0333-2","article-title":"FSGS: From pathogenesis to the histological lesion","volume":"29","author":"Angioi","year":"2016","journal-title":"J. Nephrol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1007\/s00467-019-04282-y","article-title":"Variations of type IV collagen-encoding genes in patients with histological diagnosis of focal segmental glomerulosclerosis","volume":"35","author":"Demir","year":"2020","journal-title":"Pediatr. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1159\/000508099","article-title":"Focal Segmental Glomerulosclerosis: State-of-the-Art and Clinical Perspective","volume":"144","author":"Shabaka","year":"2020","journal-title":"Nephron"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"F532","DOI":"10.1152\/ajprenal.00223.2013","article-title":"Myosin 1e is a component of the glomerular slit diaphragm complex that regulates actin reorganization during cell-cell contact formation in podocytes","volume":"305","author":"Bi","year":"2013","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"F1099","DOI":"10.1152\/ajprenal.00251.2012","article-title":"Podocyte-specific knockout of myosin 1e disrupts glomerular filtration","volume":"303","author":"Chase","year":"2012","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1056\/NEJMoa1101273","article-title":"MYO1E Mutations and Childhood Familial Focal Segmental Glomerulosclerosis","volume":"365","author":"Mele","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1681\/ASN.2019020152","article-title":"Contributions of Rare Gene Variants to Familial and Sporadic FSGS","volume":"30","author":"Wang","year":"2019","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1002\/cm.21861","article-title":"Roles of myosin 1e and the actin cytoskeleton in kidney functions and familial kidney disease","volume":"81","author":"Liu","year":"2024","journal-title":"Cytoskeleton"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.tcb.2010.04.004","article-title":"Leveraging the membrane \u2013 cytoskeleton interface with myosin-1","volume":"20","author":"McConnell","year":"2010","journal-title":"Trends Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"21514","DOI":"10.1074\/jbc.M200713200","article-title":"The Kinetic Mechanism of Myo1e (Human Myosin-IC)","volume":"277","author":"Tang","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/ki.2011.148","article-title":"Exome sequencing identified MYO1E and NEIL1 as candidate genes for human autosomal recessive steroid-resistant nephrotic syndrome","volume":"80","author":"Burgess","year":"2011","journal-title":"Kidney Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s00467-022-05634-x","article-title":"Focal segmental glomerulosclerosis and proteinuria associated with Myo1E mutations: Novel variants and histological phenotype analysis","volume":"38","author":"Krendel","year":"2023","journal-title":"Pediatr. Nephrol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e32683","DOI":"10.1097\/MD.0000000000032683","article-title":"Effect of cyclosporine A on focal segmental glomerulosclerosis caused by MYO1E mutation in a Chinese adult patient: A case report","volume":"102","author":"Li","year":"2023","journal-title":"Medicine"},{"key":"ref_14","first-page":"891","article-title":"Effects of FSGS-associated mutations on the stability and function of myosin-1 in fission yeast","volume":"8","author":"Bi","year":"2015","journal-title":"Dis. Model. Mech."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"Jcs235275","DOI":"10.1242\/jcs.235275","article-title":"Myo1e modulates the recruitment of activated B cells to inguinal lymph nodes","volume":"133","author":"Vadillo","year":"2020","journal-title":"J. Cell Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"26752","DOI":"10.1073\/pnas.1902502116","article-title":"Intermittent rolling is a defect of the extravasation cascade caused by Myosin1e-deficiency in neutrophils","volume":"116","author":"Vadillo","year":"2019","journal-title":"Proc. Natl. Acad. Sci. 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