Intragenic FMR1 disease-causing variants: a significant mutational mechanism leading to Fragile-X syndrome.

Fragile-X syndrome (FXS) is a frequent genetic form of intellectual disability (ID). The main recurrent mutagenic mechanism causing FXS is the expansion of a CGG repeat sequence in the 5'-UTR of the FMR1 gene, therefore, routinely tested in ID patients. We report here three FMR1 intragenic pathogenic variants not affecting this sequence, identified using high-throughput sequencing (HTS): a previously reported hemizygous deletion encompassing the last exon of FMR1, too small to be detected by array-CGH and inducing decreased expression of a truncated form of FMRP protein, in three brothers with ID (family 1) and two splice variants in boys with sporadic ID: a de novo variant c.990+1G>A (family 2) and a maternally inherited c.420-8A>G variant (family 3). After clinical reevaluation, the five patients presented features consistent with FXS (mean Hagerman's scores=15). We conducted a systematic review of all rare non-synonymous variants previously reported in FMR1 in ID patients and showed that six of them are convincing pathogenic variants. This study suggests that intragenic FMR1 variants, although much less frequent than CGG expansions, are a significant mutational mechanism leading to FXS and demonstrates the interest of HTS approaches to detect them in ID patients with a negative standard work-up.

[Use of complementary medicine by cancer patients in a French oncology department]. / Utilisation de médecine complémentaire chez les patients atteints de cancer dans un service de cancérologie français.

The aims of this study was to estimate and describe the reasons of use of complementary medicine in patients with a cancer treated in a French oncology department. An anonymous questionnaire was proposed to patients during treatment or follow-up in an oncology department. It was a descriptive study over 207 questionnaires. Over 195 analysable questionnaires, 34% of patients were using complementary medicine. Homeopathy (42%), plants (27%) and vitamins (18%) were the main substances used. Acupuncture (22%) and massages (15%) were the most significant techniques. No specific profile of user was observed. The main reason of using complementary medicine was not curing cancer but reducing side effects of the conventional treatment (66%). More than a half of the users of complementary medicine were not revealing their habits to their oncologist because the question was not raised in consultation. One third of cancer patients are using complementary medicine during the treatment of their disease. Complementary medicine must benefit, as well as conventional medicine, of scientific studies. The purpose of these studies should be evaluating potential benefits, toxicity and interactions with the conventional treatment in order the oncologist could warned the users. This warning could improve the confidence relationship between the oncologist and his patient.