c.1227_1228dupGG (p.Glu410Glyfs), a frequent variant in Tunisian patients with MUTYH associated polyposis

Kdissa, Ameni; Brusgaard, Klaus; Ksiaa, Mahdi; Golli, L.; Hallara, Olfa; Ousager, Lilian Bomme; Manoubi, Wiem; Seghaier, Rihab Ben; Adala, Labiba; Halleb, Yosra; Saâd, Ali; Hmila, Fahmi; Gribaa, Moez

doi:10.1016/j.cancergen.2019.10.007

Cited by 4 publications

(1 citation statement)

References 57 publications

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“…Other pathogenic MUTYH variants that may be specific to certain ethnic groups include p.(Tyr104Ter), p.(Glu466Ter), p.(Glu480del) and c.1227_1228dup p.(Glu410GLyfsX43) in Pakistani, Indian, Italian and Portuguese populations, respectively (4,(13)(14)(15). The variant c.1227_1228dup has also been found in high frequency in North African patients (16)(17)(18).…”

Section: Variant Pathogenicitymentioning

confidence: 99%

Phenotype correlations with pathogenic DNA variants in theMUTYHgene

Thet,

Plazzer,

Capella

et al. 2024

Preprint

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MUTYH-associated polyposis (MAP) is an autosomal recessive disorder where the inheritance of constitutional biallelic pathogenicMUTYHvariants predisposes a person to the development of adenomas and colorectal cancer (CRC). It is also associated with extracolonic and extraintestinal manifestations that may overlap with the phenotype of familial adenomatous polyposis (FAP). Currently, there are discrepancies in the literature regarding whether certain phenotypes are truly associated with MAP. This narrative review aims to explore the phenotypic spectrum of MAP to better characterise the MAP phenotype. A literature search was conducted to identify articles reporting on MAP-specific phenotypes. Clinical data from 2109 MAP patients identified from the literature showed that 1123 patients (53.2%) had CRC. Some patients with CRC had no associated adenomas, suggesting that adenomas are not an obligatory component of MAP. Carriers of the two missense founder variants, and possibly truncating variants, had an increased cancer risk when compared to those who carry other pathogenic variants. It has been suggested that somatic G:C>T:A transversions are a mutational signature of MAP, and could be used as a biomarker in screening and identifying patients with atypical MAP, or in associating certain phenotypes with MAP. The extracolonic and extraintestinal manifestations that have been associated with MAP include duodenal adenomas, duodenal cancer, fundic gland polyps, gastric cancer, ovarian cancer, bladder cancer and skin cancer. The association of breast cancer and endometrial cancer with MAP remains disputed. Desmoids and Congenital Hypertrophy of the Retinal Pigment Epithelium (CHRPEs) are rarely reported in MAP, but have long been seen in FAP patients, and thus could act as a distinguishing feature between the two. This collection of MAP phenotypes will assist in the assessment of pathogenicMUTYHvariants using the American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) Variant Interpretation Guidelines, and ultimately improve patient care.

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