Proteinuric renal disease

Gene: LAMA5

I don't know

Three further families published this year, though note the authors refer to the variants as VOUS.

Created: 8 Aug 2019, 4:28 a.m. | Last Modified: 8 Aug 2019, 4:28 a.m.

Panel Version: 1.221

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nephrotic syndrome

Publications

• 29534211

Red List (low evidence)

Comment on list classification: Changing the rating of this gene to Amber. 3 cases with homozygous missense variants reported but authors classify as VUS as there is no experimental evidence to link the impact of these genetic variants on protein function to disease pathogenesis.

Created: 9 Oct 2019, 10:57 a.m. | Last Modified: 9 Oct 2019, 10:57 a.m.

Panel Version: 1.223

Not associated with a phenotype in OMIM or Gene2Phenotype.

PMID: 29534211 - Braun et al 2019 - performed WES in 335 individuals of 300 families with Nephrotic syndrome and identified recessive mutations in the gene LAMA5 in three unrelated consanguineous families with childhood-onset NS that responded to immunosuppressive therapy. The 3 families were from Turkey, Egypt and Saudia Arabia and the following 3 missense variants were found - family A4389: c.2239 C >T, p.Arg747Trp, family B150: c.3002 A>G, p.Glu1001Gly, family B1284: c.8842 G>A, p.Gly2948Ser. There is evolutionary conservation at these sites. In two families, the parents were shown to be heterozygous for the variants. None of the three variants has been reported in the homozygous state in databases of healthy control populations (EVS and gnomAD) although individuals of Middle Eastern descent are poorly represented in these databases. The authors state that because experimental evidence is lacking, the impact of these genetic variants on protein function and disease pathogenesis cannot be judged with certainty.

Created: 14 Aug 2019, 4:31 p.m. | Last Modified: 14 Aug 2019, 4:39 p.m.

Panel Version: 1.221

This gene was part of an initial gene list collated by Elizabeth Watson, North Bristol NHS Trust, February 2019 on behalf of the GMS Renal Specialist Test Group. Gene Symbol submitted: LAMA5; Suggested initial gene rating: red; Evidence for inclusion: PMID: 29534211; Other comments: One published patient with paediatric nephrotic syndrome and VUS in LAMA5, plus one possible case (unpublished) identified by nephrotic syndrome research group (personal communication).

Created: 4 Feb 2019, 10:41 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
No OMIM disease association

Publications

• PMID: 29534211