Table 1.
Demographic, clinical phenotype, and genetic findings
| Patient no. (sex) | Origin | Age of onset (yr) | Clinical phenotype | Extraintestinal involvement | Surgical treatment | Genetic findings | Family history of colorectal cancer and colorectal polyposis | Familial cosegregation | Classification Verdict by: Franklina; VarSomeb Commercial laboratory |
| 1 (female) | Ashkenazi Jewish | 40–50 | 10 adenomas (right colon) + small gastric hyperplastic polyps | Pancreas SB-IPMN | None | SMAD4 (NM_005359.6):c.403C>T p.R135* | No | De novo | Pathogenic; PathogenicPathogenic |
| 2 (female) | Sephardic Jewish | 40–50 | Left-sided CRC + <10 adenomas | None | Left hemicolectomy | BMPR1A (NM_004329.3):c.675G>A p.L225= | First degree: CRC, polyposis Second degree: CRC |
Yes | Likely pathogenic; Pathogenic Likely pathogenic |
| 3 (male) | Sephardic Jewish | 20–30 | ∼40 adenomas (whole colon, advanced) | None | None |
BMPR1A (NM_004329.3): del ex1-13 Chr10: 86875867–89041308[hg19] |
First degree: CRC, polyposis Second degree: N/A |
Yes | Pathogenic; Pathogenic Pathogenic |
| 4 (female) | Sephardic Jewish | 20–30 | ∼20 adenomas (right colon) | None | None |
BMPR1A (NM_004329.3):del ex3-13 chr10:88611882-89041308[hg19] |
First degree: CRC, polyposis Second degree: CRC, polyposis |
Unknown | Pathogenic; Likely pathogenic Pathogenic |
| 5 (male) | Ashkenazi Jewish | 30–40 | Left-sided CRC + ∼20 adenomas (whole colon, advanced) | None | Total proctocolectomy with IPAA | SMAD4 (NM_005359.6):c.746A>C p.Q249P | Second degree: CRC, gastric carcinoma | Yes | VUS; Benign VUS |
| 6 (female) | Ashkenazi Jewish | 10–20 | ∼20 adenomas (whole colon, advanced) | None | Total proctocolectomy with IPAA | BMPR1A (NM_004329.3):c.388T>C p.C130R | First degree: CRC Second degree: CRC |
Yes | Likely pathogenic; VUS VUS |
| 7 (male) | Ashkenazi Jewish | 40–50 | Right-sided CRC + 10 adenomas (ascending and transverse colon, advanced) | None | Subtotal colectomy | BMPR1A (NM_004329.3):c.760C>T p.R254C | First degree: CRC Second degree: CRC |
Yes No |
VUS; VUS VUS |
| FANCI (MN_001376911.1):c.1856T>A p.L619Q | |||||||||
| VUS; VUS VUS | |||||||||
| 8 (female) | Ashkenazi Jewish | 50–60 | ∼20 adenomas (whole colon, advanced) | Papilla of Vater carcinoma | Whipple procedure | BMPR1A (NM_004329.3):c.676G>T p.V226F | First degree: CRC Second degree: CRC |
Unknown | VUS; VUS VUS |
CRC, colorectal cancer; IPAA, ileal pouch anal anastomosis; SB-IPMN, side branch intraductal papillary mucinous neoplasm; VUS, variant of unknown significance.
a
Franklin: gene-specific artificial intelligence-based variant search engine, by Genoox.
b
VarSome: the human genomic variant search engine.