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Mutations in LAMB2 Are Associated With Albuminuria and Optic Nerve Hypoplasia With Hypopituitarism.

ABSTRACT: CONTEXT:Mutations in LAMB2, encoding the basement membrane protein, laminin ?2, 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 ?2 expression compared to control kidney and a thin basement membrane on electron microscopy. Laminin ?2 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.

SUBMITTER: Tahoun M

PROVIDER: S-EPMC7048679 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Mutations in LAMB2 Are Associated With Albuminuria and Optic Nerve Hypoplasia With Hypopituitarism.

Tahoun Mona M Chandler Jennifer C JC Ashton Emma E Haston Scott S Hannan Athia A Kim Ji Soo JS D'Arco Felipe F Bockenhauer D D Anderson G G Lin Meei-Hua MH Marzouk Salah S Saied Marwa H MH Miner Jeffrey H JH Dattani Mehul T MT Waters Aoife M AM

The Journal of clinical endocrinology and metabolism 20200301 3

<h4>Context</h4>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).<h4>Case description</h4>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 h ...[more]

PMID: 31769495

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Project description:PurposeTo investigate the optic nerve and macular morphology in patients with optic nerve hypoplasia (ONH) using spectral-domain optical coherence tomography (SD OCT).DesignProspective, cross-sectional, observational study.SubjectsA total of 16 participants with ONH (10 female and 6 male; mean age, 17.2 years; 6 bilateral involvement) and 32 gender-, age-, ethnicity-, and refraction-matched healthy controls.MethodsHigh-resolution SD OCT (Copernicus [Optopol Technology S.A., Zawiercie, Poland], 3 μm resolution) and handheld SD OCT (Bioptigen Inc [Research Triangle Park, NC], 2.6 μm resolution) devices were used to acquire horizontal scans through the center of the optic disc and macula.Main outcome measuresHorizontal optic disc/cup and rim diameters, cup depth, peripapillary retinal nerve fiber layer (RNFL), and thickness of individual retinal layers in participants with ONH and in controls.ResultsPatients with ONH had significantly smaller discs (P < 0.03 and P < 0.001 compared with unaffected eye and healthy controls, respectively), horizontal cup diameter (P < 0.02 for both), and cup depth (P < 0.02 and P < 0.01, respectively). In the macula, significantly thinner RNFL (nasally), ganglion cell layer (GCL) (nasally and temporally), inner plexiform layer (IPL) (nasally), outer nuclear layer (ONL) (nasally), and inner segment (centrally and temporally) were found in patients with ONH compared with the control group (P < 0.05 for all comparisons). Continuation of significantly thicker GCL, IPL, and outer plexiform layer in the central retinal area (i.e., foveal hypoplasia) was found in more than 80% of patients with ONH. Clinically unaffected fellow eyes of patients with ONH showed mild features of underdevelopment. Visual acuity and presence of septo-optic dysplasia were associated with changes in GCL and IPL. Sensitivity and specificity for the detection of ONH based on disc and retinal optical coherence tomography (OCT) parameters were >80%.ConclusionsOur study provides evidence of retinal changes in ONH. In addition to thinning of retina layers mainly involving the RNFL and GCL, signs reminiscent of foveal hypoplasia were observed in patients with ONH. Optic nerve and foveal parameters measured using OCT showed high sensitivity and specificity for detecting ONH, demonstrating their useful for clinical diagnosis.

Dataset Information

Mutations in LAMB2 Are Associated With Albuminuria and Optic Nerve Hypoplasia With Hypopituitarism.

Publications

Mutations in LAMB2 Are Associated With Albuminuria and Optic Nerve Hypoplasia With Hypopituitarism.

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