Colorectal adenomatous polyposis Associated with MYH mutations: genotype and phenotype characteristics.
OBJECTIVE
Recent literature reports that several digestive diseases are associated with mutations in the base excision repair gene MYH. This study was designed to establish the prevalence of germ-line MYH mutations in a series of 56 consecutive patients with no detectable APC mutation and describe the phenotype of those with MYH mutations.


METHODS
MYH mutations were screened by DNA sequencing after polymerase chain reaction amplification of each exon. Clinical, endoscopic, and surgical data were collected for the tested patients.


RESULTS
MYH mutations were identified only in the group of patients with attenuated adenomatous polyposis with ten or more adenomatous polyps. The prevalence of MYH mutations was 34.4 percent (11 cases) in this subgroup of 30 patients. There were two homozygotes and eight compound heterozygotes. Only one patient had a monoallelic mutation. At least one of two mutational hot spots was identified in ten patients. Three patients presented with a family history of adenomatous polyposis in siblings, without vertical transmission. The median number of colorectal adenomatous polyps was 53 without preferential localization. Colorectal cancer was associated with polyposis in seven patients. Gastric and duodenal adenomas were diagnosed in one case. Ten of 11 patients underwent colectomy.


CONCLUSIONS
MYH mutations have been observed in one-third of patients with attenuated polyposis. The phenotype of the disease is similar to attenuated familial adenomatous polyposis. Upper gastrointestinal endoscopy also should be recommended. However, its transmission shows evidence of a recessive pattern.
Bouguen
Guillaume
G
Service des maladies de l'appareil digestif, Centre Hospitalier Universitaire Pontchaillou, 2 rue Henri Le Guilloux, Rennes, France. gbouguen@free.fr
Manfredi
Sylvain
S
Blayau
Martine
M
Dugast
Catherine
C
Buecher
Bruno
B
Bonneau
Dominique
D
Siproudhis
Laurent
L
David
Véronique
V
Bretagne
Jean-François
JF
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D045647:DNA Glycosylases / Q000235:genetics*; D005260:Female; D017491:Genes, APC; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction
D045647:DNA Glycosylases