Mutated MCM9 is associated with predisposition to hereditary mixed polyposis and colorectal cancer in addition to primary ovarian failure

Goldberg, Yael; Halpern, Naama; Hubert, Ayala; Adler, Samuel N.; Cohen, Sherri; Plesser-Duvdevani, Morasha; Pappo, Orit; Shaag, Avraham; Meiner, Vardiella

doi:10.1016/j.cancergen.2015.10.001

Cited by 59 publications

(59 citation statements)

References 19 publications

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“…The analysis of a few cohorts of 46,XX POI patients by means of high throughput techniques, such as comparative genomic hybridization array (array-CGH) and SNP array, has led to the identification of CNVs affecting several X-linked and autosomal loci with a possible role in female fertility (24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). Similarly, the recent application of whole-exome sequencing (WES) to a few POI multigenerational familial cases has succeeded in revealing rare single nucleotide variants affecting genes implicated in ovarian function (35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48). As already reported in other complex diseases characterized by a great genetic heterogeneity, it is likely that patients with POI may harbor multiple genetic variants.…”

Section: The Heterogeneous Manifestations and Multifactorial Origin Omentioning

confidence: 99%

Genetics of primary ovarian insufficiency

et al. 2016

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Primary ovarian insufficiency (POI) is characterized by a loss of ovarian function before the age of 40 and account for one major cause of female infertility. POI relevance is continuously growing because of the increasing number of women desiring conception beyond 30 years of age, when POI prevalence is >1%. POI is highly heterogeneous and can present with ovarian dysgenesis and primary amenorrhea, or with secondary amenorrhea, and it can be associated with other congenital or acquired abnormalities. In most cases POI remains classified as idiopathic. However, the age of menopause is an inheritable trait and POI has a strong genetic component. This is confirmed by the existence of several candidate genes, experimental and natural models. The variable expressivity of POI defect may indicate that, this disease may frequently be considered as a multifactorial or oligogenic defect. The most common genetic contributors to POI are the X chromosome‐linked defects. Here, we review the principal X‐linked and autosomal genes involved in syndromic and non‐syndromic forms of POI with the expectation that this list will soon be upgraded, thus allowing the possibility to predict the risk of an early age at menopause in families with POI.

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Section: The Heterogeneous Manifestations and Multifactorial Origin Omentioning

confidence: 99%

Genetics of primary ovarian insufficiency

et al. 2016

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“…Minichromosome maintenance (MCM) proteins play a role in initiating DNA replication [14]. MCM9 encodes DNA helicase which facilitates cellular mismatch repair [14].…”

Section: Mcm9 Mutationmentioning

confidence: 99%

“…Additionally, the MCM8-MCM9 complex is crucial in maintenance of the replication fork as well as double strand break repair. A genome mapping study was done by Goldberg et al [14] in two consanguineous Ashkenazi sisters who developed mixed polyposis and metastatic CRC at an early age. Results revealed that a homozygous c.672_673delGGinsC mutation in MCM9 (chr6:119243200) was present in both sisters, while other healthy family members were heterozygous.…”

Section: Mcm9 Mutationmentioning

confidence: 99%

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Updates on the Molecular Genetics of Colorectal Cancer

Wong¹,

Xie²

2017

Colorec Cancer

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Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. Although definitive therapies for advanced disease are still lacking, rapid progress has been made in the last decade in understanding the molecular mechanisms underlying CRC tumorigenesis and progression. In this review, we summarize the most recent findings in the molecular genetics of CRC with a focus on gene mutations and epigenetic changes that were identified in CRC patients.

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“…[13][14][15]. The proband homozygous for c.672_673delGGinsC also developed early-onset CRC and mixed polyposis, and three heterozygous relatives had an attenuated phenotype of late CRC or few polyps [15], indicating a potential role for perturbed MCM9 function contributing to the development of CRC.…”

Section: Introductionmentioning

confidence: 96%

Pathogenic germline MCM9 variants are rare in Australian Lynch-like syndrome patients

et al. 2016

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Highlights First screen of MCM9 for germline variants in Lynch-like syndrome patients. Fifteen variants identified in a cohort of 109 Lynch-like syndrome patients. Variants included 6 common SNPs and 9 variants of unknown significance. with LLS and variants were cross-referenced with three population-based databases (dbSNP144, 1000 Genomes, ExAC). The functional effect of variants was assessed in silico with PolyPhen-2, SIFT and CONDEL. Fifteen variants that included six common SNPs and nine variants of unknown significance (VUS) were identified.. We conclude that VUS occur in MCM9 in a small proportion of LLS patients and MCM9 mutations are unlikely to explain most LLS cases.

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Mutated MCM9 is associated with predisposition to hereditary mixed polyposis and colorectal cancer in addition to primary ovarian failure

Cited by 59 publications

References 19 publications

Genetics of primary ovarian insufficiency

Genetics of primary ovarian insufficiency

Updates on the Molecular Genetics of Colorectal Cancer

Pathogenic germline MCM9 variants are rare in Australian Lynch-like syndrome patients

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