{Reference Type}: Journal Article
{Title}: Previously reported CCDC26 risk variant and novel germline variants in GALNT13, AR, and MYO10 associated with familial glioma in Finland.
{Author}: Nurminen R;Afyounian E;Paunu N;Katainen R;Isomäki M;Nurminen A;Scaravilli M;Tolppanen J;Fey V;Kivinen A;Helén P;Välimäki N;Kesseli J;Aaltonen LA;Haapasalo H;Nykter M;Rautajoki KJ;
{Journal}: Sci Rep
{Volume}: 14
{Issue}: 1
{Year}: 2024 05 21
{Factor}: 4.996
{DOI}: 10.1038/s41598-024-62296-5
{Abstract}: Predisposing factors underlying familial aggregation of non-syndromic gliomas are still to be uncovered. Whole-exome sequencing was performed in four Finnish families with brain tumors to identify rare predisposing variants. A total of 417 detected exome variants and 102 previously reported glioma-related variants were further genotyped in 19 Finnish families with brain tumors using targeted sequencing. Rare damaging variants in GALNT13, MYO10 and AR were identified. Two families carried either c.553C>T (R185C) or c.1214T>A (L405Q) on GALNT13. Variant c.553C>T is located on the substrate-binding site of GALNT13. AR c.2180G>T (R727L), which is located on a ligand-binding domain of AR, was detected in two families, one of which also carried a GALNT13 variant. MYO10 c.4448A>G (N1483S) was detected in two families and c.1511C>T (A504V) variant was detected in one family. Both variants are located on functional domains related to MYO10 activity in filopodia formation. In addition, affected cases in six families carried a known glioma risk variant rs55705857 in CCDC26 and low-risk glioma variants. These novel findings indicate polygenic inheritance of familial glioma in Finland and increase our understanding of the genetic contribution to familial glioma susceptibility.