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'Mutations in LAMB2 associate with albuminuria and Optic Nerve Hypoplasia with Hypopituitarism'

Tahoun, M; Chandler, JC; Ashton, E; Haston, S; Hannan, A; Kim, JS; D'Arco, F; ... Waters, AM; + view all (2019) 'Mutations in LAMB2 associate with albuminuria and Optic Nerve Hypoplasia with Hypopituitarism'. The Journal of Clinical Endrocrinology & Metabolism , 105 (3) pp. 595-599. 10.1210/clinem/dgz216. Green open access

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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 twelve year old boy with short stature, visual impairment and developmental delay who presented with macroscopic haematuria and albuminuria. He had isolated growth hormone deficiency, optic nerve hypoplasia and a small anterior pituitary with corpus callosum dysgenesis on his cranial MRI, 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.

Type: Article
Title: 'Mutations in LAMB2 associate with albuminuria and Optic Nerve Hypoplasia with Hypopituitarism'
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1210/clinem/dgz216
Publisher version: https://doi.org/10.1210/clinem/dgz216
Language: English
Additional information: Copyright © Endocrine Society 2019. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: LAMB2, Optic Nerve Hypoplasia Syndrome, Pierson Syndrome
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10087082
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