Subject(s)
Hypoglycemic Agents/adverse effects , Insulin/analogs & derivatives , Lipodystrophy/chemically induced , Adolescent , Diabetes Mellitus, Type 1/drug therapy , Female , Humans , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Insulin/adverse effects , Insulin AspartABSTRACT
Silver-Russell syndrome (SRS) is characterised by prenatal and postnatal growth retardation, dysmorphic facial features, and body asymmetry. In 35-60% of SRS cases the paternally methylated imprinting control region (ICR) upstream of the H19 gene (H19-ICR) is hypomethylated, leading to downregulation of IGF2 and bi-allelic expression of H19. H19 and IGF2 are reciprocally imprinted genes on chromosome 11p15. The expression is regulated by the imprinted methylation of the ICR, which modulates the transcription of H19 and IGF2 facilitated by enhancers downstream of H19. A promoter element of IGF2, IGF2P0, is differentially methylated equivalently to the H19-ICR, though in a small number of SRS cases this association is disrupted--that is, hypomethylation affects either H19-ICR or IGF2P0. Three pedigrees associated with hypomethylation of IGF2P0 in the probands are presented here, two with paternally derived deletions, and one with a balanced translocation of inferred paternal origin. They all have a breakpoint within the H19/IGF2 enhancer region. One proband has severe growth retardation, the others have SRS. This is the first report of paternally derived structural chromosomal mutations in 11p15 causing SRS. These cases define a novel aetiology of the growth retardation in SRS, namely, dissociation of IGF2 from its enhancers.
Subject(s)
Enhancer Elements, Genetic/genetics , Gene Deletion , Gene Rearrangement/genetics , Insulin-Like Growth Factor II/genetics , RNA, Untranslated/genetics , Silver-Russell Syndrome/genetics , Adult , Alleles , Child, Preschool , Chromosome Aberrations , Chromosomes, Human, Pair 11 , Female , Gene Order , Humans , Infant , Male , RNA, Long NoncodingABSTRACT
UNLABELLED: The use of complementary/alternative medicine (CAM) is increasing. The aim was to characterise the use of CAM among patients in a paediatric department. All patients (aged 0-18 years), out-patients or hospitalised, in contact with the Department of Paediatrics, Odense University Hospital during a 2 week period in the autumn of 2001 were asked to participate. In total, 622 (92%) patients participated. The data were collected in an interviewer administered questionnaire during a short structured interview with the patient and parents. CAM was divided into herbal medicine (herbal drugs or dietary supplements) (HM), alternative therapy (AT) (i.e. acupuncture) or chiropractic (CHI). Of all patients, 53% had tried CAM at least once and 23% had tried CAM within the last month (15% HM, 7% AT and 2% CHI). There was no correlation between use of CAM and gender, age or if the patient was out-patient or hospitalised. The users were pre-school children. HM (Bio-Strath and Echinacea) was especially used to strengthen the immune system. Among AT, reflexological treatment was the most popular treatment. The most frequent users of CAM were patients with asthma, eczema or allergy plus patients suffering from gastrointestinal diseases or hospitalised for observation. More than 50% of the users experienced positive effects and 6% had side-effects from AM. Of the CAM users, 11% or 2% of the total paediatric population used CAM instead of conventional medicines. CONCLUSION: Of the paediatric patients, 53% had tried complementary/alternative medicine, which was used as a supplement to conventional medicine although we did not know how long it was used. Paediatric patients should be interviewed about their use of complementary/alternative medicine with regard to side-effects, interactions or lack of compliance with conventional medicine.
