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- Title
Mutations in LAMB2 Are Associated With Albuminuria and Optic Nerve Hypoplasia With Hypopituitarism.
- Authors
Tahoun, Mona; Chandler, Jennifer C; Ashton, Emma; Haston, Scott; Hannan, Athia; Kim, Ji Soo; D'Arco, Felipe; Bockenhauer, D; Anderson, G; Lin, Meei-Hua; Marzouk, Salah; Saied, Marwa H; Miner, Jeffrey H; Dattani, Mehul; Waters, Aoife M; Dattani, Mehul T
- Abstract
<bold>Context: </bold>Mutations in LAMB2, encoding the basement membrane protein, laminin β2, are associated with an autosomal recessive disorder characterized by congenital nephrotic syndrome, ocular abnormalities, and neurodevelopmental delay (Pierson syndrome).<bold>Case Description: </bold>This report describes a 12-year-old boy with short stature, visual impairment, and developmental delay who presented with macroscopic hematuria and albuminuria. He had isolated growth hormone deficiency, optic nerve hypoplasia, and a small anterior pituitary with corpus callosum dysgenesis on his cranial magnetic resonance imaging, thereby supporting a diagnosis of optic nerve hypoplasia syndrome. Renal histopathology revealed focal segmental glomerulosclerosis. Using next-generation sequencing on a targeted gene panel for steroid-resistant nephrotic syndrome, compound heterozygous missense mutations were identified in LAMB2 (c.737G>A p.Arg246Gln, c.3982G>C p.Gly1328Arg). Immunohistochemical analysis revealed reduced glomerular laminin β2 expression compared to control kidney and a thin basement membrane on electron microscopy. Laminin β2 is expressed during pituitary development and Lamb2-/- mice exhibit stunted growth, abnormal neural retinae, and here we show, abnormal parenchyma of the anterior pituitary gland.<bold>Conclusion: </bold>We propose that patients with genetically undefined optic nerve hypoplasia syndrome should be screened for albuminuria and, if present, screened for mutations in LAMB2.
- Subjects
OPTIC nerve; PITUITARY gland; CONGENITAL disorders; PITUITARY dwarfism; FOCAL segmental glomerulosclerosis; HYPOPITUITARISM; RECESSIVE genes; PITUITARY hormones
- Publication
Journal of Clinical Endocrinology & Metabolism, 2019, pN.PAG
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/clinem/dgz216