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Mutations in LAMB2 are associated with albuminuria and optic nerve hypoplasia with hypopituitarism
- 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.
- Subjects :
- Male
Pathology
medicine.medical_specialty
LAMB2
Endocrinology, Diabetes and Metabolism
Clinical Biochemistry
Case Report
Hypopituitarism
Compound heterozygosity
Biochemistry
Short stature
03 medical and health sciences
0302 clinical medicine
Endocrinology
Focal segmental glomerulosclerosis
Anterior pituitary
Internal medicine
medicine
Albuminuria
Humans
Optic Nerve Hypoplasia
Child
Congenital nephrotic syndrome
030304 developmental biology
2. Zero hunger
0303 health sciences
Optic nerve hypoplasia
business.industry
Biochemistry (medical)
medicine.disease
3. Good health
Phenotype
medicine.anatomical_structure
optic nerve hypoplasia syndrome
Pierson syndrome
Mutation
Laminin
medicine.symptom
business
Nephrotic syndrome
030217 neurology & neurosurgery
Subjects
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