The first mutations in the MYH gene reported in Moroccan colon cancer patients.

BACKGROUND: Biallelic germline mutations in the MYH gene cause MYH-associated polyposis (MAP) disease, an autosomal recessive form of inherited colorectal cancer. People with MAP tend to develop attenuated multiple adenomatous colon polyps during their lifetime and will have an increased risk of colorectal cancer. Contrary to familial adenomatous polyposis, the number of adenomas is often lower in MAP (from 5 to 100), and even some patients have recently been reported with no identified adenomas. There have been many investigations into MAP that have been conducted in many different countries. Currently there is limited data on MAP in Morocco, and it is reasonable to think, that the prevalence of this form of genetic predisposition is as high as other autosomal recessive genetic diseases found in countries with high rates of consanguinity. The aim of this study is to examine the frequency of MYH mutations in colorectal cancer and/or attenuated polyposis in Moroccan patients. PATIENTS AND METHODS: The study population consisted of 62 patients; 52 with colorectal cancer, three of them had attenuated polyposis (2 to 99 adenomatous polyps). 10 other patients were referred to our department for polyposis without colorectal cancer. We carried out DNA analysis in 62 patients to screen for the three recurrent mutations c.494A>G (p.Tyr165Cys), c.1145G>A (p.Gly382Asp) and c.1185_1186dup, p.Glu396GlyfsX43, whereas 40 subjects were screened for germline MYH mutations in the whole coding sequence of the MYH gene by direct DNA sequencing. All these 40 patients, except two, had colorectal cancer without polyposis. RESULTS: Three patients with colorectal cancer and attenuated polyposis carried biallelic mutations in the MUTYH gene one with the c.494 A>G mutation, one with the c.1105delC mutation, one with the c.1145G>A mutation. One patient with 25 adenomas without colorectal cancer carried the c.1145G>A mutation at a homozygote state and one patient with 3 polyps was heterozygote for the mutation c.1145G>A. No biallelic mutations of MYH gene were detected in colorectal cancer patients and in patients with small number (<5) of polyps without colorectal cancer. CONCLUSION: We report the first biallelic MYH mutations in four Moroccan patients with clinical criteria of MAP; three of them had colorectal cancer with attenuated polyposis. No MYH mutations were found in colorectal patients without polyposis. Despite the relatively small sample size of the current study, our findings suggest that the MAP is not a frequent cause of colon cancer in Morocco as we had expected, and the molecular analysis of MYH gene should be restricted to patients displaying the classical phenotype of MAP.

[Evaluation of the vagal activity by the Deep-Breathing test]. / Evaluation de l'activité vagale par le test de la respiration profonde (Deep-Breathing).

OBJECTIVE: The Deep-Breathing (DB) test is of major importance in the evaluation of the vagal response (VR). We applied this test to assess the VR in a group of subjects with functional (neurological, cardiovascular or digestive) symptoms unexplained by standard cardiac examination and to compare it with the VR measured in a group of healthy controls. PATIENTS AND METHODS: The following groups were considered: a C-Group of healthy controls (n=50), and three groups each consisting of 50 symptomatic patients (S1, S2, S3). Subjects in the S1-Group had a postural orthostatic tachycardia syndrome (POTS), while members of the S2-Group had arterial hypertension, and members of S3-Group had neither POTS nor arterial hypertension. The VR was expressed as a percentage variation of RR intervals 100x[(RR(max)-RR(min))/RR(min)], and was correlated with age and sex in the C-Group before any comparison. RESULTS: In controls the VR was 31.0%+/-8.2. It was negatively correlated with age (r=-0.42, p=0.003) and there was no significant difference between males (31.2%+/-5.7) and females (30.9%+/-9.0) (p=0.12). Compared to the C-Group, the VR was 51.6%+/-20.4 in the S1-Group (p<0.001), 26.9%+/-11.3 in the S2-Group (p<0.001), and 47.2%+/-22.7 in the S3-Group (p<0.001). CONCLUSION: The VR was independent of sex but was negatively correlated with age. In comparison with healthy controls, it was significantly increased in the patients with POTS and significantly decreased in hypertensives.