This website provides information on patients with mutations in the LAMB2 gene, including clinical data, molecular data, management and research options.

The syndrome caused by mutations in the LAMB2 gene is a multisystem disorder with Autosomal recessive (AR) inheritance: Nephrotic syndrome type 5, with or without ocular abnormalities (MIM614199) or Pierson syndrome (MIM609049). Here they are called LAMB2-nephropathy. Clinical features include proteinuria or nephrotic syndrome (severe proteinuria) often with an onset in the neonatal period and resulting in kidney failure requiring a kidney transplant before one year of age; which are sometimes accompanied by ocular and neuromuscular abnormalities. Ocular abnormalities include microcoria, nystagmus, strabismus, myopia, cataracts, retinitis pigmentosa, and optic nerve hypoplasia. Neuromuscular abnormalities include muscular hypotonia, psychomotor disability and blindness. However there is also an increasing number of people diagnosed with biallelic LAMB2 mutations who have milder disease with a later onset of nephrotic syndrome and kidney failure, and often without the ophthalmic or muscular complications.

In general, the proteinuria and nephrotic syndrome do not respond to steroid treatment or immunosuppression but instead the proteinuria responds to ACE inhibition which may delay the onset of kidney failure. The ocular and muscle abnormalities must be treated symptomatically but while a squint may be treated, often a cure is not possible.

The LAMB2 gene codes for the β2 chain of the Laminin α5β2γ1 (laminin521) molecule which is the major laminin component of the basement membranes in the glomerulus, the muscles and the eye.

Pathogenic variants in LAMB2 are truncating (nonsense, frameshift, deletions, insertions, rearrangements, and splice site changes) and non-truncating (missense and in-frame variants). In general, two truncating variants are associated with a worse prognosis than one truncating and one missense variant. Although mutations in the LN domain (residues Ser43 to Asn282) of the laminin β2 chain have been reported to be more common and associated with a more severe prognosis, this has not been confirmed in a recent study.

This website was created to share and collect information about clinic, management and research projects to gather more knowledge and provide better treatment of patients with mutations in the LAMB2 gene.

Prof Judy Savige, MBBS, PhD, The University of Melbourne, Department of Medicine (Melbourne Health and Northern Health), Melbourne, Australia, j.savige@unimelb.edu.au