LAMA5 was first reported in relation to autosomal recessive LAMA5-related multisystemic syndrome in 2013 (Chatterjee et al., PMID: 24130771). LAMA5—related multisystemic syndrome is a complex syndrome with a wide spectrum of symptoms involving renal (exclusive at times) phenotypes. 16 variants (missense and nonsense) that have been reported in 11 probands in 9 publications (PMIDs: 24130771, 28544784, 29534211, 31130284, 31680349, 31937884, 32439764, 33242826, 35584218) are included in this curation. The mechanism of pathogenicity is reported to be LOF. This gene-disease association is also supported by experimental evidence (animal models, expression studies, and biochemical function) (PMIDs: 10625553, 20150535, 35584218). Multiple animal models capitulate a multisystemic phenotype with evidence of renal involvement, supported by expression studies in the glomerular basement membrane (GBM) and LAMA5’s importance in GBM integrity. In summary, LAMA5 is definitively associated with autosomal recessive LAMA5-related multisystemic syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Glomerulopathy GCEP on the meeting date April 26th, 2022 (SOP Version 8).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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