Biallelic germline mutations in MAD1L1 induce a syndrome of aneuploidy with high tumor susceptibility
Germline mutations leading to aneuploidy are rare, and their tumor-promoting properties are
mostly unknown at the molecular level. We report here novel germline biallelic mutations in
MAD1L1, encoding the spindle assembly checkpoint (SAC) protein MAD1, in a 36-year-old
female with a dozen of neoplasias. Functional studies demonstrated lack of full-length
protein and deficient SAC response, resulting in~ 30 to 40% of aneuploid blood cells. Single-
cell RNA analysis identified mitochondrial stress accompanied by systemic inflammation …
mostly unknown at the molecular level. We report here novel germline biallelic mutations in
MAD1L1, encoding the spindle assembly checkpoint (SAC) protein MAD1, in a 36-year-old
female with a dozen of neoplasias. Functional studies demonstrated lack of full-length
protein and deficient SAC response, resulting in~ 30 to 40% of aneuploid blood cells. Single-
cell RNA analysis identified mitochondrial stress accompanied by systemic inflammation …
Bilallelic germline mutations in MAD1L1 induce a novel syndrome of aneuploidy with high tumor susceptibility
C Villarroya-Beltri, A Osorio, R Torres-Ruiz… - bioRxiv, 2022 - biorxiv.org
Aneuploidy is a frequent feature of human tumors. Germline mutations leading to aneuploidy
are very rare in humans, and their tumor-promoting properties are mostly unknown at the
molecular level. We report here novel germline biallelic mutations in MAD1L1, the gene
encoding the Spindle Assembly Checkpoint (SAC) protein MAD1, in a 36-year-old female
with a dozen of neoplasias, including five malignant tumors. Functional studies in peripheral
blood cells demonstrated lack of full-length protein and deficient SAC response, resulting …
are very rare in humans, and their tumor-promoting properties are mostly unknown at the
molecular level. We report here novel germline biallelic mutations in MAD1L1, the gene
encoding the Spindle Assembly Checkpoint (SAC) protein MAD1, in a 36-year-old female
with a dozen of neoplasias, including five malignant tumors. Functional studies in peripheral
blood cells demonstrated lack of full-length protein and deficient SAC response, resulting …
