[Clinical characterization and genetic analysis of two Chinese pedigrees affected with Familial adenomatous polyposis caused by variants of MUTYH gene].
To explore the clinical phenotypes and genetic characteristics of two patients with Familial adenomatous polyposis (FAP) due to variants of MUTYH gene.
Two patients presenting with multiple colorectal polyps on gastrointestinal endoscopy at Xinxiang Central Hospital respectively in June and October 2022 were selected as study subjects. A retrospective study design was employed to collect their clinical data and summarize their clinical and genetic features. Whole exome sequencing (WES) was carried out for both patients. Candidate variants were validated by Sanger sequencing of their family members. Bioinformatic analysis was conducted for the candidate variants. Pathogenicity of the variants was assessed based on the guidelines from American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital [Ethics No.: 2024-282-01 (K)].
Patient 1 was a 7-year-old girl who presented with "pigmentation on the lips, buccal mucosa, hard palate, eyelids and fingers for 5 years." Colonoscopy revealed multiple colonic polyps. WES revealed that she has harbored compound heterozygous variants of the MUTYH gene, namely c.857G>A (p.Gly286Glu) and c.1118C>T (p.Ala373Val), which were inherited from her mother and father, respectively. Based on the ACMG guidelines, the variants were classified as pathogenic (PS4+PM1+PM2_Supporting+PP3) and variant of uncertain significance (VUS) (PM2_Supporting+PP3), respectively. Patient 2 was a 42-year-old male who presented with "increased frequency of bowel movements for 2 month." Colonoscopy revealed multiple colorectal polyps. WES revealed that he has harbored compound heterozygous variants of the MUTYH gene, namely c.53C>T (p.Pro18Leu) and c.880C>T (p.Arg294Cys), which were inherited from his father and mother, respectively. Based on the ACMG guidelines, the variants were classified as likely pathogenic (PS4+PM1+PM2_Supporting+PP3) and VUS (PM2_Supporting+PM1), respectively.
Compound heterozygous variants of the MUTYH gene probably underlay the pathogenesis of FAP in these patients. Above findings have enriched the mutational spectrum of the MUTYH gene.
Two patients presenting with multiple colorectal polyps on gastrointestinal endoscopy at Xinxiang Central Hospital respectively in June and October 2022 were selected as study subjects. A retrospective study design was employed to collect their clinical data and summarize their clinical and genetic features. Whole exome sequencing (WES) was carried out for both patients. Candidate variants were validated by Sanger sequencing of their family members. Bioinformatic analysis was conducted for the candidate variants. Pathogenicity of the variants was assessed based on the guidelines from American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital [Ethics No.: 2024-282-01 (K)].
Patient 1 was a 7-year-old girl who presented with "pigmentation on the lips, buccal mucosa, hard palate, eyelids and fingers for 5 years." Colonoscopy revealed multiple colonic polyps. WES revealed that she has harbored compound heterozygous variants of the MUTYH gene, namely c.857G>A (p.Gly286Glu) and c.1118C>T (p.Ala373Val), which were inherited from her mother and father, respectively. Based on the ACMG guidelines, the variants were classified as pathogenic (PS4+PM1+PM2_Supporting+PP3) and variant of uncertain significance (VUS) (PM2_Supporting+PP3), respectively. Patient 2 was a 42-year-old male who presented with "increased frequency of bowel movements for 2 month." Colonoscopy revealed multiple colorectal polyps. WES revealed that he has harbored compound heterozygous variants of the MUTYH gene, namely c.53C>T (p.Pro18Leu) and c.880C>T (p.Arg294Cys), which were inherited from his father and mother, respectively. Based on the ACMG guidelines, the variants were classified as likely pathogenic (PS4+PM1+PM2_Supporting+PP3) and VUS (PM2_Supporting+PM1), respectively.
Compound heterozygous variants of the MUTYH gene probably underlay the pathogenesis of FAP in these patients. Above findings have enriched the mutational spectrum of the MUTYH gene.