Targeted next-generation sequencing approach for molecular genetic diagnosis of hereditary colorectal cancer: Identification of a novel single nucleotide germline insertion in adenomatous polyposis coli gene causes familial adenomatous polyposis.


BACKGROUND:Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disease which primarily manifested with developing adenomas or polyps in colon or rectum. It is caused by the germline mutations in adenomatous polyposis coli (APC) gene. Patients with FAP are usually manifested with "hundreds or even thousands" adenomas or polyps in colon or rectum. However, without proper clinical diagnosis and timely surgical interventions, colorectal adenomas, or polyps gradually increase in size and in numbers which finally leads to colorectal cancer (CRC) at the mean age of 36 years of the patient. METHODS:In this study, we identified a family with FAP. In this family, FAP has been diagnosed clinically based on symptoms, medical test reports, and positive family history for three generations. In order to unveil the molecular genetic consequences underlying the disease phenotype, we performed next-generation sequencing with a customized and designed panel of genes reported to be associated with hereditary CRC. The variant identified by next-generation sequencing has been validated by Sanger sequencing. RESULTS:A heterozygous novel insertion [c.3992_3993insA; p.Thr1332Asnfs*10] in exon 16 of APC gene has been identified. This novel insertion is cosegregated well with the FAP phenotype among all the affected members of this family. This mutation causes a frameshift by the formation of a premature stop codon which finally results in the formation of a truncated APC protein of 1,342 amino acids instead of the wild type APC protein of 2,843 amino acids. Hence, this is a loss-of-function mutation. This mutation was not found in unaffected family members or in normal control individuals. CONCLUSION:Our present study emphasizes the importance of a novel approach of the gene panel-based high-throughput sequencing technology for easy and rapid screening for patients with FAP or CRC which will help the clinician for follow-up and management.


Mol Genet Genomic Med


Wang D,Liang S,Zhang X,Dey SK,Li Y,Xu C,Yu Y,Li M,Zhao G,Zhang Z




Has Abstract


2019-01-01 00:00:00










  • Analysis of expression levels of markers associated with tumor proliferation and angiogenesis in familial adenomatous polyposis.

    abstract:BACKGROUND:Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary disease with colorectal adenomatous polyps as the main clinical manifestations. The objective of this study was to analyze and compare the expression levels of tumor proliferation and angiogenesis-related genes in different tissue secti...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Zhang Z,Wang D,Xu C,Li Y,Yu Y,Chen C,Li M,Zhang X

    更新日期:2020-12-01 00:00:00

  • An update of pathogenic variants in ASPM, WDR62, CDK5RAP2, STIL, CENPJ, and CEP135 underlying autosomal recessive primary microcephaly in 32 consanguineous families from Pakistan.

    abstract:BACKGROUND:Primary microcephaly (MCPH) is a congenital neurodevelopmental disorder manifesting as small brain and intellectual disability. It underlies isolated reduction of the cerebral cortex that is reminiscent of early hominids which makes it suitable model disease to study the hominin-specific volumetric expansion...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Rasool S,Baig JM,Moawia A,Ahmad I,Iqbal M,Waseem SS,Asif M,Abdullah U,Makhdoom EUH,Kaygusuz E,Zakaria M,Ramzan S,Haque SU,Mir A,Anjum I,Fiaz M,Ali Z,Tariq M,Saba N,Hussain W,Budde B,Irshad S,Noegel AA,Höning

    更新日期:2020-09-01 00:00:00

  • Targeted regions sequencing identified four novel PNPLA1 mutations in two Chinese families with autosomal recessive congenital ichthyosis.

    abstract:BACKGROUND:Autosomal recessive congenital ichthyosis (ARCI) is a rare genetically heterogeneous cutaneous disease predominantly characterized by erythroderma, generalized abnormal scaling of the whole body and a collodion membrane at birth. Numerous causative genes have been demonstrated to be responsible for ARCI incl...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Li L,Liu W,Xu Y,Li M,Tang Q,Yu B,Cai R,Liu S

    更新日期:2020-02-01 00:00:00

  • A de novo heterozygous variant in the SON gene is associated with Zhu-Tokita-Takenouchi-Kim syndrome.

    abstract:BACKGROUND:Zhu-Tokita-Takenouchi-Kim (ZTTK, OMIM# 617140) syndrome is a rare, autosomal dominant genetic disorder caused by heterozygous variants in the SON gene (OMIM#182465, GenBank#NC_000021.9). There are only 33 cases and 26 causative SON variants reported to date since the first report in 2015. Here, we report a n...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Yang L,Yang F

    更新日期:2020-11-01 00:00:00

  • Phenylketonuria in Portugal: Genotype-phenotype correlations using molecular, biochemical, and haplotypic analyses.

    abstract:BACKGROUND:The impairment of the hepatic enzyme phenylalanine hydroxylase (PAH) causes elevation of phenylalanine levels in blood and other body fluids resulting in the most common inborn error of amino acid metabolism (phenylketonuria). Persistently high levels of phenylalanine lead to irreversible damage to the nervo...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Ferreira F,Azevedo L,Neiva R,Sousa C,Fonseca H,Marcão A,Rocha H,Carmona C,Ramos S,Bandeira A,Martins E,Campos T,Rodrigues E,Garcia P,Diogo L,Ferreira AC,Sequeira S,Silva F,Rodrigues L,Gaspar A,Janeiro P,Amorim A

    更新日期:2021-01-19 00:00:00

  • Founder mutation in KCNJ10 in Pakistani patients with EAST syndrome.

    abstract:BACKGROUND:EAST syndrome is an autosomal recessive disorder caused by loss-of-function mutations in the gene KCNJ10. Among the 14 pathogenic mutations described so far, the p.R65P mutation stands out as the most frequent one and is particularly associated with patients of Pakistani origin. As a result we aimed to estab...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Abdelhadi O,Iancu D,Tekman M,Stanescu H,Bockenhauer D,Kleta R

    更新日期:2016-06-07 00:00:00

  • Two tSNPs in BRIP1 are associated with breast cancer during TDT analysis.

    abstract:OBJECTIVES:This study aimed to investigate and confirm the association between 15 single nucleotide polymorphisms of four susceptibility genes (NBS1, TP53, PTEN, and BRIP1) and the susceptibility of breast cancer. METHODS:The genome DNA was extracted from peripheral blood and tumor tissues from one hundred and sevente...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Li X,Li Z,Yang M,Luo Y,Hu L,Xiao Z,Huang A,Huang J

    更新日期:2021-01-05 00:00:00

  • A de novo variant in the X-linked gene CNKSR2 is associated with seizures and mild intellectual disability in a female patient.

    abstract:BACKGROUND:Eight different deletions and point variants of the X-chromosomal gene CNKSR2 have been reported in families with males presenting intellectual disability (ID) and epilepsy. Obligate carrier females with a frameshift variant in the N-terminal protein coding part of CNKSR2 or with a deletion of the complete g...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Polla DL,Saunders HR,de Vries BBA,van Bokhoven H,de Brouwer APM

    更新日期:2019-10-01 00:00:00

  • Genetic structure and forensic characterization of 36 Y-chromosomal STR loci in Tibeto-Burman-speaking Yi population.

    abstract:BACKGROUND:Male-specifically inherited Y-STRs have been widely used in population genetics and forensic investigations. METHODS:We genotyped and analyzed Y chromosome haplotypes of 408 unrelated Tibeto-Burman-speaking Yi male individuals from Guizhou using Goldeneye® Y-PLUS kit. Population comparisons between the Guiz...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Song Z,Wang Q,Zhang H,Tang J,Wang Q,Zhang H,Yang M,Ji J,Ren Z,Wu Y,Huang J

    更新日期:2021-01-15 00:00:00

  • Penetrance and expressivity of the R858H CACNA1C variant in a five-generation pedigree segregating an arrhythmogenic channelopathy.

    abstract:BACKGROUND:Isolated cardiac arrhythmia due to a variant in CACNA1C is of recent knowledge. Most reports have been of singleton cases or of quite small families, and estimates of penetrance and expressivity have been difficult to obtain. We here describe a large pedigree, from which such estimates have been calculated. ...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Gardner RJM,Crozier IG,Binfield AL,Love DR,Lehnert K,Gibson K,Lintott CJ,Snell RG,Jacobsen JC,Jones PP,Waddell-Smith KE,Kennedy MA,Skinner JR

    更新日期:2019-01-01 00:00:00

  • A rapid and reliable chromosome analysis method for products of conception using interphase nuclei.

    abstract:BACKGROUND:Karyotype determination has a central role in the genetic workup of pregnancy loss, as aneuploidy (trisomy and monosomy) and polyploidy (triploidy and tetraploidy) are the cause in at least 50% of first trimester, 25% of second trimester, and 11% of third trimester miscarriages. There are several limitations...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Babu R,Van Dyke DL,Bhattacharya S,Dev VG,Liu M,Kwon M,Gu G,Koduru P,Rao N,Williamson C,Fuentes E,Fuentes S,Papa S,Kopuri S,Lal V

    更新日期:2018-05-01 00:00:00

  • Two rare PROX1 variants in patients with lymphedema.

    abstract:BACKGROUND:The PROX1 gene is specifically expressed in a subpopulation of endothelial cells that, by budding and sprouting, give rise to the lymphatic system. It also plays a critical role in neurogenesis and during development of many organs, such as the eye lens, liver, and pancreas. METHODS:We used next-generation ...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Ricci M,Amato B,Barati S,Compagna R,Veselenyiova D,Kenanoglu S,Stuppia L,Beccari T,Baglivo M,Kurti D,Krajcovic J,Serrani R,Dundar M,Basha SH,Chiurazzi P,Bertelli M

    更新日期:2020-10-01 00:00:00

  • Modification effect of sex and obesity on the correlation of LEP polymorphisms with leptin levels in Taiwanese obese women.

    abstract:BACKGROUND:Obesity has become the main health issue in developed countries as it impacts life expectancy and increases mortality of cerebrovascular or cardiovascular diseases. The leptin is one of the adipokines which presents in the serum in proportion to the amount of adipose tissue and is translated from LEP gene. I...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Duan DM,Jhang JY,Wu S,Teng MS,Hsu LA,Ko YL

    更新日期:2020-03-01 00:00:00

  • Significant association between RETN genetic polymorphisms and alcohol-induced osteonecrosis of femoral head.

    abstract:BACKGROUND:Alcohol-induced osteonecrosis of femoral head (ONFH) is a complex disease and genetic factors are one of the causes. The purpose of this study is to investigate the effects of RETN (resistin; OMIM: 605565) and LDLR (low density lipoprotein receptor; OMIM: 606945) polymorphisms on the risk of alcohol-induced ...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Liu C,An F,Cao Y,Wang J,Tian Y,Wu H,Wang J

    更新日期:2019-08-01 00:00:00

  • Quality improvement of clinic flow for complex genetic conditions: Using Ehlers-Danlos syndrome as a model.

    abstract:BACKGROUND:Genetic providers face the challenge of having adequate time to conduct a comprehensive evaluation. Hypermobile Ehlers-Danlos (hEDS) syndrome has a complex array of symptoms. An initial visit can involve approximately 60-80 min and an additional 45 min for the check-in and checkout process. We propose a mode...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Prakash P,Eble TN,Dhar SU

    更新日期:2018-11-01 00:00:00

  • Investigation on the role of biallelic variants in VEGF-C found in a patient affected by Milroy-like lymphedema.

    abstract:BACKGROUND:Milroy-like disease is the diagnostic definition used for patients with phenotypes that resemble classic Milroy disease (MD) but are negative to genetic testing for FLT4. In this study, we aimed at performing a genetic characterization and biochemical analysis of VEGF-C variations found in a female proband b...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Mukenge S,Jha SK,Catena M,Manara E,Leppänen VM,Lenti E,Negrini D,Bertelli M,Brendolan A,Jeltsch M,Aldrighetti L

    更新日期:2020-09-01 00:00:00

  • Two novel mutations identified in familial cases with Donohue syndrome.

    abstract::Donohue syndrome (DS) is a rare and lethal autosomal recessive disease caused by mutations in the insulin receptor (INSR) gene, manifesting marked insulin resistance, severe growth retardation, hypertrichosis, and characteristic dysmorphic features. We report the clinical, molecular, and biochemical characterization o...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Falik Zaccai TC,Kalfon L,Klar A,Elisha MB,Hurvitz H,Weingarten G,Chechik E,Fleisher Sheffer V,Haj Yahya R,Meidan G,Gross-Kieselstein E,Bauman D,Hershkovitz S,Yaron Y,Orr-Urtreger A,Wertheimer E

    更新日期:2014-01-01 00:00:00

  • Identifying gene mutations of Chinese patients with polycystic kidney disease through targeted next-generation sequencing technology.

    abstract:BACKGROUND:Polycystic kidney disease (PKD) is the most common hereditary kidney disease. The main mutational genes causing autosomal dominant polycystic kidney disease (ADPKD) are PKD1 and PKD2 as well as some rare pathogenic genes. Unilateral PKD is rare in clinics, and its association with gene mutations is unclear. ...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Wang T,Li Q,Shang S,Geng G,Xie Y,Cai G,Chen X

    更新日期:2019-06-01 00:00:00

  • Integrated bioinformatics analysis of key genes involved in progress of colon cancer.

    abstract:BACKGROUND:Colon cancer is one of most malignant cancers around worldwide. Nearly 20% patients were diagnosed at colon cancer with metastasis. However, the lack of understanding regarding its pathogenesis brings difficulties to study it. METHODS:In this study, we acquired high-sequence data from GEO dataset, and perfo...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Yang H,Wu J,Zhang J,Yang Z,Jin W,Li Y,Jin L,Yin L,Liu H,Wang Z

    更新日期:2019-04-01 00:00:00

  • Cytogenetic and FISH analysis of 93 multiple myeloma Moroccan patients.

    abstract:BACKGROUND:Multiple myeloma (MM) is a disease characterized by heterogeneous clinical presentations as well as complex genetic and molecular abnormalities. In MM, cytogenetic analysis is a challenge because of the low proliferation of malignant plasma cells. Thus, interphase fluorescence in situ hybridization (FISH), p...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Hamdaoui H,Benlarroubia O,Ait Boujmia OK,Mossafa H,Ouldim K,Belkhayat A,Smyej I,Benrahma H,Dehbi H,Chegdani F

    更新日期:2020-09-01 00:00:00

  • Establishment of the Alabama Hereditary Cancer Cohort - strategies for the inclusion of underrepresented populations in cancer genetics research.

    abstract:BACKGROUND:Historically, groups that are most susceptible to health and healthcare disparities have been underrepresented in medical research. It is imperative to explore approaches that can facilitate the recruitment of underrepresented individuals into research studies. METHODS:Two approaches, hospital and community...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 临床试验,杂志文章,多中心研究


    authors: Bishop MR,Shah A,Shively M,Huskey ALW,Omeler SM,Bilgili EP,Jackson E,Daniell K,Stallworth E,Spina S,Shepp K,Bergstresser S,Davis A,Dean H,Gibson J,Johnson B,Merner ND

    更新日期:2018-09-01 00:00:00

  • Pharmacogenomics: From classroom to practice.

    abstract::Perceptions and challenges connecting Pharmacogenomics taught in classrooms and translationing it to advance pharmacy practice rotations and healthcare settings and potential areas of development. ...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 社论


    authors: Nutter SC,Gálvez-Peralta M

    更新日期:2018-05-01 00:00:00

  • Weighted gene coexpression network analysis identifies a new biomarker of CENPF for prediction disease prognosis and progression in nonmuscle invasive bladder cancer.

    abstract:BACKGROUND:The dreadful prognosis of nonmuscle invasive bladder cancer mainly results from the delay in recognition of individuals with a high risk of progression. Thus, the emphasis of this work lies in developing valuable biomarkers that is conducive to accurately predicting the progression of NMIBC. METHODS:Microar...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Shi J,Zhang P,Liu L,Min X,Xiao Y

    更新日期:2019-11-01 00:00:00

  • A comprehensive assessment of Next-Generation Sequencing variants validation using a secondary technology.

    abstract:BACKGROUND:Recently, increasing innovations improved the accuracy of next generation sequencing (NGS) data. However, the validation of all NGS variants increased the cost and turn-around time of clinical diagnosis, and therefore limited the further development of clinical applications. We aimed to comprehensively asses...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Zheng J,Zhang H,Banerjee S,Li Y,Zhou J,Yang Q,Tan X,Han P,Fu Q,Cui X,Yuan Y,Zhang M,Shen R,Song H,Zhang X,Zhao L,Peng Z,Wang W,Yin Y

    更新日期:2019-07-01 00:00:00

  • The phenotype-driven computational analysis yields clinical diagnosis for patients with atypical manifestations of known intellectual disability syndromes.

    abstract:BACKGROUND:Due to extensive clinical and genetic heterogeneity of intellectual disability (ID) syndromes, the process of diagnosis is very challenging even for expert clinicians. Despite recent advancements in molecular diagnostics methodologies, a significant fraction of ID patients remains without a clinical diagnosi...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Jezela-Stanek A,Ciara E,Jurkiewicz D,Kucharczyk M,Jędrzejowska M,Chrzanowska KH,Krajewska-Walasek M,Żemojtel T

    更新日期:2020-09-01 00:00:00

  • Forensic characteristics and phylogenetic analyses of one branch of Tai-Kadai language-speaking Hainan Hlai (Ha Hlai) via 23 autosomal STRs included in the Huaxia™ Platinum System.

    abstract:BACKGROUND:Hainan Island, located in the South China Sea and separated from the Leizhou Peninsula by Qiongzhou Strait, is the second largest island after Taiwan in China. With the expansion of Han Chinese and the gradual formation of "South Hlai and North Han", nowadays, Hainan Hlai is the second largest population aft...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Li W,Wang X,Wang X,Wang F,Du Z,Fu F,Wu W,Wang S,Mu Z,Chen C,Hu X,Ding J,Meng Y,Qiu P,Fan H

    更新日期:2020-10-01 00:00:00

  • Identification of histone malonylation in the human fetal brain and implications for diabetes-induced neural tube defects.

    abstract:BACKGROUND:Neural tube defects (NTDs) are severe congenital malformations. Diabetes during pregnancy is a risk factor for NTDs, but its mechanism remains elusive. Emerging evidence suggests that protein malonylation is involved in diabetes. Here, we report the correlation between histone lysine malonylation in diabetes...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Zhang Q,Cai T,Xiao Z,Li D,Wan C,Cui X,Bai B

    更新日期:2020-09-01 00:00:00

  • A novel prognostic model based on multi-omics features predicts the prognosis of colon cancer patients.

    abstract:BACKGROUND:As a common malignant tumor in the colon, colon cancer (CC) has high incidence and recurrence rates. This study is designed to build a prognostic model for CC. METHODS:The gene expression dataset, microRNA-seq dataset, copy number variation (CNV) dataset, DNA methylation dataset, and transcription factor (T...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Yang H,Jin W,Liu H,Wang X,Wu J,Gan D,Cui C,Han Y,Han C,Wang Z

    更新日期:2020-07-01 00:00:00

  • Clinical implementation of gene panel testing for lysosomal storage diseases.

    abstract:BACKGROUND:The diagnostic workup in patients with a clinical suspicion of lysosomal storage diseases (LSD) is often difficult due to the variability in the clinical phenotype. The gold standard for diagnosis of LSDs consists of enzymatic testing. However, due to the sequential nature of this methodology and inconsisten...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Gheldof A,Seneca S,Stouffs K,Lissens W,Jansen A,Laeremans H,Verloo P,Schoonjans AS,Meuwissen M,Barca D,Martens G,De Meirleir L

    更新日期:2019-02-01 00:00:00

  • Consumer use and response to online third-party raw DNA interpretation services.

    abstract:BACKGROUND:With the availability of raw DNA generated from direct-to-consumer (DTC) testing companies, there has been a proliferation of third-party online services that are available to interpret the raw data for both genealogy and/or health purposes. This study examines the current landscape and downstream clinical i...

    journal_title:Molecular genetics & genomic medicine

    pub_type: 杂志文章


    authors: Wang C,Cahill TJ,Parlato A,Wertz B,Zhong Q,Cunningham TN,Cummings JJ

    更新日期:2018-01-01 00:00:00