European journal of human genetics : EJHG
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Eur. J. Hum. Genet. · Nov 2013
Citizens' perspectives on personalized medicine: a qualitative public deliberation study.
Our objective was to explore citizens' informed and reasoned values and expectations of personalized medicine, a timely yet novel genomics policy issue. A qualitative, public deliberation study was undertaken using a citizens' reference panel on health technologies, established to provide input to the health technology assessment process in Ontario, Canada. The citizens' panel consisted of five women and nine men, aged 18-71 years, with one member selected from each health authority region. ⋯ Concerned that personalized tests might be used to ration care, they suggested that treatment should be made available if patients wanted it, irrespective of tests that indicate little benefit. This issue raises clinical and policy challenges that may undermine the value of personalized medicine. Further efforts to deliberate with the public are warranted to inform effective, efficient and equitable translation of personalized medicine.
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Eur. J. Hum. Genet. · Oct 2013
Phenotypic spectrum and prevalence of INPP5E mutations in Joubert syndrome and related disorders.
Joubert syndrome and related disorders (JSRD) are clinically and genetically heterogeneous ciliopathies sharing a peculiar midbrain-hindbrain malformation known as the 'molar tooth sign'. To date, 19 causative genes have been identified, all coding for proteins of the primary cilium. There is clinical and genetic overlap with other ciliopathies, in particular with Meckel syndrome (MKS), that is allelic to JSRD at nine distinct loci. ⋯ The most common clinical presentation among mutated families (7/11, 64%) was Joubert syndrome with ocular involvement (either progressive retinopathy and/or colobomas), while the remaining cases had pure JS. Kidney, liver and skeletal involvement were not observed. None of the MKS fetuses carried INPP5E mutations, indicating that the two ciliopathies are not allelic at this locus.
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Eur. J. Hum. Genet. · Apr 2013
Case ReportsA familial case of alveolar capillary dysplasia with misalignment of pulmonary veins supports paternal imprinting of FOXF1 in human.
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare developmental lung disorder that is uniformly lethal. Affected infants die within the first few weeks of their life despite aggressive treatment, although a few cases of late manifestation and longer survival have been reported. We have shown previously that mutations and deletions in FOXF1 are a cause of this disorder. ⋯ The two tested affected siblings share the same chromosome 16 haplotype inherited from their maternal grandfather. Their single healthy sibling has a different chromosome 16 haplotype inherited from the maternal grandmother. The results are consistent with paternal imprinting of FOXF1 in human.
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Congenital heart defects affect 60-85% of patients with RASopathies. We analysed the clinical and molecular characteristics of atrioventricular canal defect in patients with mutations affecting genes coding for proteins with role in the RAS/MAPK pathway. Between 2002 and 2011, 101 patients with cardiac defect and a molecularly confirmed RASopathy were collected. ⋯ In conclusion, our data confirm previous reports indicating that atrioventricular canal defect represents a relatively common feature in Noonan syndrome. Among RASopathies, atrioventricular canal defect was observed to occur with higher prevalence among subjects with PTPN11 mutations, even though this association was not significant possibly because of low statistical power. Familial segregation of atrioventricular canal defect should be considered in the genetic counselling of families with RASopathies.