A syndrome comprising childhood-onset glomerular kidney disease and ocular abnormalities with progressive loss of vision is caused by mutated LAMB2

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2006-11, Vol.21 (11), p.3283-3286
• Main Authors: Matejas, Verena, Al-Gazali, Lihadh, Amirlak, Iradj, Zenker, Martin
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age of Onset; Amino Acid Sequence; Amino Acid Substitution - genetics; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; autosomal recessive; Biological and medical sciences; blindness; Child; Child, Preschool; Disease Progression; Emergency and intensive care: renal failure. Dialysis management; Eye Abnormalities - genetics; Eye Abnormalities - pathology; Female; Glomerulonephritis; Humans; Intensive care medicine; Kidneys; laminin; Laminin - genetics; Male; Medical sciences; Molecular Sequence Data; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; nephrotic syndrome; Nephrotic Syndrome - genetics; Nephrotic Syndrome - pathology; Pedigree; Phenotype; Pierson syndrome; Tumors of the urinary system; Vision Disorders - genetics; Vision Disorders - pathology
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfl463

Background. Pierson syndrome (OMIM 609049) is a severe congenital oculorenal disorder with early lethality. The condition is caused by mutations in the LAMB2 gene leading to complete loss of function of the gene product laminin β2, an essential component of the glomerular and other basement membranes. Methods. We present a non-consanguineous family with seven offspring affected by childhood-onset nephrotic syndrome progressing to end-stage renal failure and ocular abnormalities including cataracts, anterior chamber and iris abnormalities, and progressive blindness due to retinal detachment. The LAMB2 gene was analysed in this family by direct sequencing. Results. The disorder turned out to segregate with compound heterozygosity for two novel LAMB2 mutations, ▵V79 and Q1728X. Whereas the mutation Q1728X is predicted to confer complete loss of function, ▵V79 probably represents a hypomorphic allele, thus explaining the substantially milder phenotype in this family. Conclusion. This observation demonstrates that the phenotypic spectrum of LAMB2-associated disorders is broader than previously anticipated, and suggests that milder, non-lethal phenotypes may be associated with mutations retaining some residual function.