The search for the gene for Silver-Russell syndrome

Patients with Silver-Russell syndrome display intrauterine growth restriction and other dysmorphic features. No single genetic cause for this syndrome has been found, although there are a small number of familial cases and some patients with chromosomal rearragements. Maternal uniparental disomy of chromosome 7 has been found in approximately 7% of patients with Silver-Russell syndrome. In five of these patients exhibiting maternal uniparental disomy, no common regions of isodisomy were found, thereby ruling out the expression of a recessive allele. It is most likely that one or more imprinted genes are responsible for the phenotype of Silver-Russell syndrome. Human chromosome 7 demonstrates homology with two imprinted regions on mouse chromosomes 6 and 11, which are equivalent to human chromosome regions 7q32 and 7p11–p13, respectively. We directly analysed the imprinting status of candidate genes from chromosome 7 that mapped to homologous imprinted regions in the mouse and also had a potential role in growth. The candidates were the genes that encode the epidermal growth factor receptor and the insulin-like growth binding proteins-1 and -3. All three of these candidate genes are localized to chromosome region 7p11–p13. Using intragenic polymorphisms as markers, we found that all three genes showed biallelic expression in different fetal tissues. Therefore, it is unlikely that these candidate genes are directly involved in producing the phenotype of Silver-Russell syndrome. Other candidates are under analysis, including two newly identified genes that are known to be imprinted.     

Vaccination for the paediatrician

In most of Australia, general practitioners manage routine childhood vaccination schedules. However, paediatricians have an important role and need to have a thorough understanding of vaccination, particularly as it interfaces with other medical care. This is challenging as the Australian Standard Vaccination Schedule has undergone some substantial changes over the past 4 years, with the addition of meningococcal C conjugate, 7 valent pneumococcal conjugate, varicella and inactivated polio vaccines. Paediatricians are frequently the first port of call for advice on vaccination schedules for children with special needs, in relation to either vaccine efficacy or the risk of side effects. Categories include children with a range of chronic diseases, immunosuppression, premature infants and immigrant children. Advice about specific vaccines such as varicella, inactivated polio, influenza or multivalent vaccines and revaccination after adverse events is also often sought. The aim of this article is to update paediatricians on vaccination recommendations and relevant reference sources. The first part of this article discusses groups with special vaccination requirements. The second part discusses the use of individual vaccines in these children.     

The search for the gene for Silver-Russell syndrome

Patients with Silver-Russell syndrome display intrauterine growth restriction and other dysmorphic features. No single genetic cause for this syndrome has been found, although there are a small number of familial cases and some patients with chromosomal rearrangements. Maternal uniparental disomy of chromosome 7 has been found in approximately 7% of patients with Silver-Russell syndrome. In five of these patients exhibiting maternal uniparental disomy, no common regions of isodisomy were found, thereby ruling out the expression of a recessive allele. It is most likely that one or more imprinted genes are responsible for the phenotype of Silver-Russell syndrome. Human chromosome 7 demonstrates homology with two imprinted regions on mouse chromosomes 6 and 11, which are equivalent to human chromosome regions 7q32 and 7p11-p13, respectively. We directly analysed the imprinting status of candidate genes from chromosome 7 that mapped to homologous imprinted regions in the mouse and also had a potential role in growth. The candidates were the genes that encode the epidermal growth factor receptor and the insulin-like growth factor binding proteins-1 and -3. All three of these candidate genes are localized to chromosome region 7p11-p13. Using intragenic polymorphisms as markers, we found that all three genes showed biallelic expression in different fetal tissues. Therefore, it is unlikely that these candidate genes are directly involved in producing the phenotype of Silver-Russell syndrome. Other candidates are under analysis, including two newly identified genes that are known to be imprinted.     

News for the Practitioner

News for the Practitioner     

News for the Practitioner

Conclusions In infants, the DTP-HbOC-combination was safe and more mmunogenic than separate DTP/HbOC injections.