GLMN (Glomulin)

Note	There is no phenotype-genotype correlation in GVM.
	Schematic representation of glomulin : The two stars (*) indicate the start and the stop codons, in exon 2 and 19 respectively. All known mutations are shown. Somatic second hit is in blue.
Germinal	To date, 29 different inherited mutations (deletions, insertions and nonsense substitutions) have been identified. The most 5' mutation are located in the first coding exon. The majority of them cause premature truncation of the protein and likely result in loss-of-function. One mutation deletes 3 nucleotides resulting in the deletion of an asparagine at position 394 of the protein. More than 70% of GVMs are caused by eight different mutations in glomulin: 157delAAGAA (40,7%), 108C>A (9,3%), 1179delCAA (8,1%), 421insT and 738insT (4,65% each), 554delA+556delCCT (3,5%), 107insG and IVS5-1(G>A) (2,3% each).
Somatic	The phenotypic variability observed in GVM could be explained by the need of a somatic second-hit mutation. Such a mechanism was discovered in one GVM (somatic mutation 980delCAGAA), suggesting that the lesion is due to a complete localized loss-of-function of glomulin. This concept can explain why some patients have bigger lesions than others, why new lesions appear, and why they are multifocal. This could also explain, why some mutation carriers are unaffected.

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