RESUMO
Ultimate advances in genetic technologies have permitted the detection of transmitted cases of congenital diseases due to parental gonadosomatic mosaicism. Regarding Cornelia de Lange syndrome (CdLS), up to date, only a few cases are known to follow this inheritance pattern. However, the high prevalence of somatic mosaicism recently reported in this syndrome (â¼13%), together with the disparity observed in tissue distribution of the causal variant, suggests that its prevalence in this disorder could be underestimated. Here, we report a new case of parental gonadosomatic mosaicism in SMC1A gene that causes inherited CdLS, in which the mother of the patient carries the causative variant in very low allele frequencies in buccal swab and blood. While the affected child presents with typical CdLS phenotype, his mother does not show any clinical manifestations. As regards SMC1A, the difficulty of clinical identification of carrier females has been already recognized, as well as the gender differences observed in CdLS expressivity when the causal variant is found in this gene. Currently, the use of DNA deep-sequencing techniques is highly recommended when it comes to molecular diagnosis of patients, as well as in co-segregation studies. These enable us to uncover gonadosomatic mosaic events in asymptomatic or oligosymptomatic parents that had been overlooked so far, which might have great implications regarding genetic counseling for recurrence risk.
RESUMO
BACKGROUND: In Europe, imported malarial cases occur in returning travelers and immigrants mostly from African countries. There have been an increasing number of cases in the past years in Spain. METHODS: An analysis of all cases of malaria who attended at the Hospital of Mostoles in the Southwest of Madrid from 1995 to 2007 was performed. Clinical, epidemiological, laboratory, and parasitological findings were analyzed and compared between immigrants coming from endemic countries (recent immigrants) and children who traveled to endemic areas to visit friends and relatives (VFRs). RESULTS: Sixty cases of imported malaria were detected. Most of the cases (59 of 60) were acquired in sub-Saharan Africa. The most common species was Plasmodium falciparum (43 of 60). Microscopic examination was positive in 95%, and the polymerase chain reaction (PCR) for Plasmodium achieved additional diagnosis in seven cases. Fourteen cases were VFRs; none of them used appropriate malaria chemoprophylaxis. Fever and thrombocytopenia were significantly more common among VFRs. They also had significantly higher parasite density. Twelve cases were asymptomatic at the time of diagnosis; all of them were recent immigrants. CONCLUSIONS: VFRs account for a significant number of childhood malarial cases. These patients had not taken malaria chemoprophylaxis and malarial cases were more severe. VFR children are a high-risk group, and pretravel advice should underline the risk for malaria. Recent immigrants can be asymptomatic and parasitemias are lower. Therefore, a high index of suspicion is necessary, and PCR for Plasmodium should be performed in case of negative thick smears.