title: Mutated MCM9 is associated with predisposition to hereditary mixed polyposis and colorectal cancer in addition to primary ovarian failure.
abstract: Mutations in MCM9, which encodes DNA helicase, were recently shown to cause a clinical phenotype of primary ovarian failure and chromosomal instability. MCM9 plays an essential role in homologous recombination-mediated double-strand break repair. We describe a multiplex family with early colorectal carcinoma and mixed polyposis associated with primary hypergonadotropic hypogonadism. A combination of whole genome homozygosity mapping as well as exome sequencing and targeted gene sequencing identified a homozygous c.672_673delGGinsC mutation that predicts a truncated protein, p.Glu225Lysfs*4. Our data expand the phenotypic spectrum of MCM9 mutations and suggest a link between MCM9 and inherited predisposition to mixed polyposis and early-onset colorectal cancer.
authors.affiliation: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. Electronic address: yaelg@hadassah.org.il.
authors.forename: Yael
authors.initials: Y
authors.lastname: Goldberg
authors.affiliation: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Naama
authors.initials: N
authors.lastname: Halpern
authors.affiliation: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Ayala
authors.initials: A
authors.lastname: Hubert
authors.affiliation: Department of Gastroenterology, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Samuel N
authors.initials: SN
authors.lastname: Adler
authors.affiliation: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Sherri
authors.initials: S
authors.lastname: Cohen
authors.affiliation: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Department of Genetics and Metabolic Diseases, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Morasha
authors.initials: M
authors.lastname: Plesser-Duvdevani
authors.affiliation: Department of Pathology, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Pappo
authors.affiliation: Department of Genetics and Metabolic Diseases, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Avraham
authors.initials: A
authors.lastname: Shaag
authors.affiliation: Department of Genetics and Metabolic Diseases, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Vardiella
authors.initials: V
authors.lastname: Meiner
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000150:complications / Q000235:genetics; D000328:Adult; D043171:Chromosomal Instability; D015179:Colorectal Neoplasms / Q000150:complications / Q000235:genetics; D003241:Consanguinity; D005260:Female; D006801:Humans; D064110:Minichromosome Maintenance Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D016649:Primary Ovarian Insufficiency / Q000150:complications / Q000235:genetics
chemical_list: C501931:MCM9 protein, human; D064110:Minichromosome Maintenance Proteins
keywords: DNA helicase MCM9; chromosomal instability; colorectal cancer; hereditary mixed polyposis; primary ovarian failure