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Mutations in LAMB2 are associated with albuminuria and optic nerve hypoplasia with hypopituitarism

Authors :
Detlef Bockenhauer
Salah Marzouk
Marwa H. Saied
Aoife M. Waters
Mona Tahoun
Jeffrey H. Miner
Mehul T. Dattani
Meei Hua Lin
Ji Soo Kim
Emma Ashton
Felipe D’Arco
Scott Haston
Athia Hannan
G. Anderson
Jennifer C. Chandler
Source :
The Journal of Clinical Endocrinology and Metabolism
Publication Year :
2020
Publisher :
Bioscientifica, 2020.

Abstract

Context 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). Case description 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. Conclusion We propose that patients with genetically undefined optic nerve hypoplasia syndrome should be screened for albuminuria and, if present, screened for mutations in LAMB2.

Details

ISSN :
16624009
Database :
OpenAIRE
Journal :
Yearbook of Paediatric Endocrinology
Accession number :
edsair.doi.dedup.....030d0f0ca46b9f88232afe4144c608b6
Full Text :
https://doi.org/10.1530/ey.17.1.3