Glioma Susceptibility 9
A number sign (#) is used with this entry because of evidence that susceptibility to glioma-9 (GLM9) is conferred by heterozygous mutation in the POT1 gene (606478) on chromosome 7q31.
Mutation in the POT1 gene can also cause susceptibility to cutaneous malignant melanoma-10 (CMM10; 615848).
For a general phenotypic description and a discussion of genetic heterogeneity of glioma, see GLM1 (137800).
Clinical FeaturesBainbridge et al. (2015) reported 3 unrelated families in which at least 2 members had adult-onset glioma, either an astrocytoma or an oligodendroglioma. In 2 families, several other family members had different cancers, including lung cancer, kidney cancer, and leukemia. None of the families had a history of melanoma.
InheritanceThe transmission pattern of GLM9 in the families reported by Bainbridge et al. (2015) was consistent with autosomal dominant inheritance and incomplete penetrance.
Molecular GeneticsIn affected members of 3 unrelated families with GLM9, Bainbridge et al. (2015) identified 3 different heterozygous mutations in the POT1 gene (606478.0009-606478.0011). Two families had members with histories of other cancers, although none had melanoma, and several unaffected family members carried the mutation, consistent with incomplete penetrance. Functional studies of the variants were not performed, but there was evidence that mutation carriers had a higher telomere content compared to those without the mutation. The families were ascertained from a larger cohort of 55 glioma families who underwent whole-exome sequencing.