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Renal involvement in patients with mucolipidosis IIIalpha/beta: Causal relation or co‐occurrence?
Author(s) -
Tüysüz Beyhan,
ErcanSencicek Adife Gülhan,
Canpolat Nur,
Koparır Asuman,
Yılmaz Saliha,
Kılıçaslan Işın,
Gülez Burcu,
Bilguvar Kaya,
Günel Murat
Publication year - 2016
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.37543
Subject(s) - medicine , lysosomal storage disease , renal biopsy , proteinuria , missense mutation , mucolipidosis , pathology , renal function , endocrinology , kidney , disease , mutation , genetics , chemistry , biology , gene , biochemistry , enzyme
Mucolipidosis IIIalpha/beta (MLIIIalpha/beta) is a rare lysosomal storage disorder characterized by childhood onset of flexion contractures of fingers, joint stiffness in the shoulders, hips, and knees, and mild short stature. Recessive mutations in the GNPTAB gene have been associated with MLIIIalpha/beta. We present five children aged 9–16 years from a large kindred family whose serum activities of several lysosomal enzymes were significantly elevated. Whole exome sequencing followed by confirmation by Sanger sequencing identified a novel homozygous missense mutation (c.22 A > G; p.R8G) in the GNPTAB gene in all affected subjects. The five patients initially presented with flexion contractures of fingers followed by stiffnes of large joints. Only two affected boys also had a nephrotic‐range proteinuria. Renal biopsy showed focal segmental glomerulosclerosis and foamy appearance of glomerular visceral epithelial cells which were compatible with storage disease. No other known causes of proteinuria could be detected by both laboratory and biopsy findings. There was no known family history of hereditary kidney disease, and healthy siblings and parents had normal renal function and urinalysis. These findings suggest that the renal involvement probably due to MLIIIalpha/beta, although it can still be present by coincidence in the two affected patients. © 2016 Wiley Periodicals, Inc.