A novel APC mutation identified in a large Chinese family with familial adenomatous polyposis and a brief literature review

Pang, Ming; Liu, Yijun; Hou, Xiaolin; Yang, Jialiang; He, Xuelai; Hou, Nengyi; Liu, Peixi; Luo, Liang; Fu, Junwen; Wang, Kang; Ye, Zimeng; Gong, Bo

doi:10.3892/mmr.2018.9130

Cited by 6 publications

(7 citation statements)

References 30 publications

(24 reference statements)

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“…However, there also might be other effects such as modifying genes or environmental factors contributing to the marked clinical variability of FAP even within families [ 5 ]. Additionally, a study in a large Chinese family with FAP reportedly identified the novel frameshift mutation c.1317delA, p.(Ala440LeufsTer14) in exon 11 of the APC gene leading to a change in protein [ 19 ]. These authors noticed that the termination in the exon 11 was correlated with extra colonic manifestations which includes duodenal polyposis and sebaceous cysts.…”

Section: Discussionmentioning

confidence: 99%

A distinct APC pathogenic germline variant identified in a southern Thai family with familial adenomatous polyposis

et al. 2021

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Background Familial adenomatous polyposis (FAP) is caused by pathogenic germline variants in the APC gene. To date, multiple pathogenic variants in coding regions, splice sites, and deep intronic regions have been revealed. However, there are still pathogenic variants that remain unidentified. Methods Twenty-nine primer pairs flanking exons 2–16 (i.e., coding exons 1–15) of APC and their exon–intron junctions were used for germline pathogenic variant screening in Southern Thai patients with familial adenomatous polyposis (FAP). Transcription analysis was performed to confirm the pathogenicity of a splice site deletion of intron 10. Family members were interviewed for clinical histories. Blood samples were collected from 18 family members for a segregation study. Subsequently, clinical data of affected members were collected from the hospital databases. Results We found a distinct heterozygous 16-bp deletion at the splice donor site of intron 10 leading to a skipping of exon 10 which was confirmed by transcript analysis (APC: c 1312 + 4_1312 + 19del, r.934_1312del). Predictive testing for the pathogenic APC variant in 18 of the proband’s family members (ten healthy and eight affected) from three generations showed the same heterozygous germline pathogenic variant in eight affected adult members (15–62 years old) and two children (7 and 10 years old). Seven of the ten carriers of the disease-causing variant had undergone colonoscopy, and colonic polyps were found in all cases, which confirmed the segregation of the inherited pathogenic variant. The phenotypic spectrum was found to vary within the family; and some affected family members exhibited extracolonic manifestations. Conclusions To our knowledge, the pathogenic APC variant, c.1312 + 4_1312 + 19del, r.934_1312del, has not previously been reported. This study is one of the few reports describing the phenotypic consequences of a pathogenic APC variant in a high number of affected family members.

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Section: Discussionmentioning

confidence: 99%

A distinct APC pathogenic germline variant identified in a southern Thai family with familial adenomatous polyposis

et al. 2021

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“…On the other hand, the finding of gastrointestinal hyperplastic polyposis could be related to genetic variant in genes such as STK11, associated with Peutz-Jeghers syndrome [35]; APC, associated with familial adenomatous polyposis [36]; and PTEN, associated to Cowden syndrome [37]; or less often in TSC1/2 genes, associated to Tuberous sclerosis complex, whose gastrointestinal manifestations are uncommon [38]. The search for variants in other genes was not possible in the patient of the present report, due to his death and not autopsy authorization.…”

Section: Discussionmentioning

confidence: 99%

Birt-Hogg-Dubé syndrome with simultaneous hyperplastic polyposis of the gastrointestinal tract: case report and review of the literature

et al. 2020

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Background: Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant genodermatosis characterized by benign growth of the hair follicles, the presence of pulmonary cysts, spontaneous pneumothorax, and bilateral renal tumors that are usually hybrid oncocytic or multifocal chromophobe renal cell carcinoma. The diagnosis is confirmed by the presence of a pathogenic variant in the tumor suppressor folliculin (FLCN) gene mapped at 17p11.2. Although the dermatological lesions typical of BHDS are benign and only cause aesthetic concerns, and the pulmonary manifestations are controllable, the greater tendency of patients with this syndrome to present benign or malignant renal tumors, often bilateral and multifocal, makes the diagnosis of this syndrome important for the prognosis of the patients. The objective was to report the case of a patient with BHDS, without pulmonary manifestations and with hyperplastic polyposis of the gastrointestinal tract, and to perform a literature review. Case presentation: A 60-year-old man complained of abdominal pain and diarrhoea for 2 months. Physical examination was normal except for the presence of normochromic papules in the frontal region of the face associated with hyperkeratotic and hyperchromic papules in the dorsal region. The excisional biopsies of the skin lesions indicated trichodiscomas. Esophagogastroduodenoscopy, enteroscopy, and colonoscopy showed the presence of hyperplastic polyps in the stomach, duodenum, jejunum, colon, and rectum. Computed tomography (CT) and magnetic resonance imaging (MRI) of the abdomen revealed multiple expansive solid lesions in both kidneys, with necrotic and calcified areas. Renal magnetic resonance angiography also showed a solid lesion in the right kidney measuring 5 cm in diameter and another solid lesion in the left kidney measuring 8 cm in diameter, both suggestive of renal angiomyolipoma. CT scans of the skull, chest, and temporal bones were normal. The genetic study revealed the presence of a variant of FLCN in the intron 13. Conclusions: To the best of our knowledge, this is the first reported case of BHDS with the simultaneous finding of gastrointestinal hyperplastic polyposis, which may represent a possible phenotypic expression of this syndrome that has not yet been described.

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“…DNA samples from the couple and the proband were analyzed using targeted NGS as reported previously (5). A customdesigned gene panel, synthesized using the Agilent SureSelect Target Enrichment technique (Agilent Technologies, Inc.), was used to capture the coding regions of 356 genes, including their exons and exon-intron boundaries (1.285 Mbp in total).…”

Section: Methodsmentioning

confidence: 99%

“…Recently, targeted exome sequencing has been successfully used to identify genes that cause Mendelian disorders (5). Together, DNA capture technology and next-generation sequencing (NGS) analysis allow for the rapid and cost-effective parallel sequencing of specific genes of interest.…”

Section: Introductionmentioning

confidence: 99%

“…Together, DNA capture technology and next-generation sequencing (NGS) analysis allow for the rapid and cost-effective parallel sequencing of specific genes of interest. In previous studies, targeted exome sequencing has been used as a tool for the molecular diagnosis of ARPKD (1,5,6). Using this approach, the present study identified two novel compound heterozygous mutations in the PKHD1 gene causing ARPKD in a Chinese family.…”

Section: Introductionmentioning

confidence: 99%

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Novel compound heterozygous PKHD1 mutations cause autosomal recessive polycystic kidney disease in a Han Chinese family

Wang

Yang

et al. 2019

Mol Med Report

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autosomal recessive polycystic kidney disease (ARPKD) is a hereditary fibrocystic disease that primarily involves the kidneys and hepatobiliary tract. The polycystic kidney and hepatic disease 1 (PKHD1) gene is the only gene implicated in ARPKD. The present study aimed to identify PKHD1 mutations causing ARPKD in a Chinese family. A couple that underwent prenatal genetic diagnosis for ARPKD and their families were recruited for the present study. Genomic DNA was collected from the amniotic fluid of the fetus (proband) and from peripheral blood of all other available family members. Targeted exome sequencing was performed on the couple and the proband, followed by direct Sanger sequencing on other family members and normal controls to confirm candidate pathogenic variants. Two novel compound heterozygous mutations in the PKHD1 gene were identified as causative in the proband, including maternally inherited c.2876C>T (p.Ser959Phe) and paternally inherited c.5772C>A (p.Phe1924Leu). Each mutation was found to co-segregate with the ARPKD phenotype in the family. Other family members either carried one of the two mutations or lacked both mutations, while the mutations were not found in 576 ethnically matched normal controls. Therefore, two novel compound heterozygous PKHD1 mutations were implicated in causing ARPKD in a Han Chinese family. The results expand the mutation spectrum of PKHD1 that leads to arPKd, which may improve genetic counseling and prenatal diagnosis for families with ARPKD.

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A novel APC mutation identified in a large Chinese family with familial adenomatous polyposis and a brief literature review

Cited by 6 publications

References 30 publications

A distinct APC pathogenic germline variant identified in a southern Thai family with familial adenomatous polyposis

A distinct APC pathogenic germline variant identified in a southern Thai family with familial adenomatous polyposis

Birt-Hogg-Dubé syndrome with simultaneous hyperplastic polyposis of the gastrointestinal tract: case report and review of the literature

Novel compound heterozygous PKHD1 mutations cause autosomal recessive polycystic kidney disease in a Han Chinese family

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