| Verf.angabe: | Verena Matejas, Bernward Hinkes, Faisal Alkandari, Lihadh Al-Gazali, Ellen Annexstad, Mehmet B. Aytac, Margaret Barrow, Květa Bláhová, Detlef Bockenhauer, Hae Il Cheong, Iwona Maruniak-Chudek, Pierre Cochat, Jörg Dötsch, Priya Gajjar, Raoul C. Hennekam, Françoise Janssen, Mikhail Kagan, Ariana Kariminejad, Markus J. Kemper, Jens Koenig, Jillene Kogan, Hester Y. Kroes, Eberhard Kuwertz-Bröking, Amy F. Lewanda, Ana Medeira, Jutta Muscheites, Patrick Niaudet, Michel Pierson, Anand Saggar, Laurie Seaver, Mohnish Suri, Alexey Tsygin, Elke Wühl, Aleksandra Zurowska, Steffen Uebe, Friedhelm Hildebrandt, Corinne Antignac, and Martin Zenker |
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| Abstract: | Mutations of LAMB2 typically cause autosomal recessive Pierson syndrome, a disorder characterized by congenital nephrotic syndrome, ocular and neurologic abnormalities, but may occasionally be associated with milder or oligosymptomatic disease variants. LAMB2 encodes the basement membrane protein laminin β2, which is incorporated in specific heterotrimeric laminin isoforms and has an expression pattern corresponding to the pattern of organ manifestations in Pierson syndrome. Herein we review all previously reported and several novel LAMB2 mutations in relation to the associated phenotype in patients from 39 unrelated families. The majority of disease-causing LAMB2 mutations are truncating, consistent with the hypothesis that loss of laminin β2 function is the molecular basis of Pierson syndrome. Although truncating mutations are distributed across the entire gene, missense mutations are clearly clustered in the N-terminal LN domain, which is important for intermolecular interactions. There is an association of missense mutations and small in frame deletions with a higher mean age at onset of renal disease and with absence of neurologic abnormalities, thus suggesting that at least some of these may represent hypomorphic alleles. Nevertheless, genotype alone does not appear to explain the full range of clinical variability, and therefore hitherto unidentified modifiers are likely to exist. Hum Mutat 31:992-1002, 2010. © 2010 Wiley-Liss, Inc. |
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