A syndrome comprising childhood-onset glomerular kidney disease and ocular abnormalities with progressive loss of vision is caused by mutated LAMB2.
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 beta2, 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, triangle upV79 and Q1728X. Whereas the mutation Q1728X is predicted to confer complete loss of function, triangle upV79 probably represents a hypomorphic allele, thus explaining the substantially milder phenotype in this family.


CONCLUSIONS
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.
Matejas
Verena
V
Institute of Human Genetics, University of Erlangen-Nuremberg, Germany.
Al-Gazali
Lihadh
L
Amirlak
Iradj
I
Zenker
Martin
M
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005124:Eye Abnormalities / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D007797:Laminin / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009404:Nephrotic Syndrome / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D014786:Vision Disorders / Q000235:genetics* / Q000473:pathology
D007797:Laminin; C058783:laminin beta2