Acromelic frontonasal dysostosis and ZSWIM6 mutation: phenotypic spectrum and mosaicism.

Acromelic frontonasal dysostosis (AFND) is a distinctive and rare frontonasal malformation that presents in combination with brain and limb abnormalities. A single recurrent heterozygous missense substitution in ZSWIM6, encoding a protein of unknown function, was previously shown to underlie this disorder in four unrelated cases. Here we describe four additional individuals from three families, comprising two sporadic subjects (one of whom had no limb malformation) and a mildly affected female with a severely affected son. In the latter family we demonstrate parental mosaicism through deep sequencing of DNA isolated from a variety of tissues, which each contain different levels of mutation. This has important implications for genetic counselling.

Mutational spectrum and phenotypes in Danish families with hereditary angioedema because of C1 inhibitor deficiency.

BACKGROUND: Hereditary angioedema (HAE), type I and II, is an autosomal dominant disease with deficiency of functional C1 inhibitor protein causing episodic swellings of skin, mucosa and viscera. HAE is a genetically heterogeneous disease with more than 200 different mutations in the SERPING1 gene. A genotype-phenotype relationship does not seem to exist in HAE, although the polymorphism c.-21T>C of exon 2 has been reported to be associated with a more severe phenotype. We aimed to establish the mutational spectrum of C1 inhibitor deficiency in Denmark and investigate the possible disease-aggravating effect of the c.-21T>C polymorphism. METHODS: Hereditary angioedema was diagnosed based on clinical features and C1 inhibitor deficiency. A general severity score ranging from 0 to 10 was developed based on age at disease onset, clinical manifestations and treatment experiences. SERPING1 gene investigation was performed by exon sequencing followed by multiplex ligation-dependent probe amplification genomic rearrangement analysis in all known Danish HAE families. RESULTS: Fifty-nine patients with HAE from 26 families were included in this study. The mean disease severity score was 7.12 [1-10], and the mean C1 inhibitor function was 26% [20-46%]. The sensitivity of the mutational screening was 96%, and 13 new mutations were found in this Danish patient cohort. Nine patients (15%) carried the c.-21T>C polymorphism, but they didn't have a more severe phenotype. CONCLUSION: Thirteen new mutations were identified in the Danish HAE population. No correlation between the c.-21T>C polymorphism, the biochemical values of C1 inhibitor function and the clinical severity score was found.

How well do patient and general practitioner agree about the content of consultations?

OBJECTIVE: To analyse agreement between patients' and general practitioners' perception of content of consultations. DESIGN: Cross-sectional study based on paired questionnaires answered by patients and general practitioners (GPs). SETTING: General practices in the County of Funen, Denmark. SUBJECTS: All 291 GPs in the County were invited to join the investigation, and 137 accepted. All patients who consulted the participating GPs in a 3 day period were included in the investigation. The GPs registered 6021 patients, of whom 3578 (59%) returned the completed questionnaire. MAIN OUTCOME MEASURES: GPs and patients were asked about the urgency of the consultation, number of problems presented, duration of consultation, and quality of communication. The GPs' and patients' answers were matched, and variables of agreement were made. Patients were furthermore asked about their satisfaction with the consultation. RESULTS AND CONCLUSION: Agreement for the four matched answers varied from 69% to 83%. Disagreement was observed more often in consultations where the patient's self-evaluated health was poor, the patient was female, had a chronic disease, expected a prescription or felt that the GP had little knowledge of his/her life circumstances. Agreement concerning urgency, number of problems and quality of communication was associated with a higher degree of patient satisfaction.