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- Gudmundsson, Sanna, et al.
(författare)
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A novel RAD21 p.(Gln592del) variant expands the clinical description of Cornelia de Lange syndrome type 4 : Review of the literature
- 2019
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Ingår i: European Journal of Medical Genetics. - : Elsevier. - 1769-7212 .- 1878-0849. ; 62:6
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Tidskriftsartikel (refereegranskat)abstract
- Cornelia de Lange syndrome (CdLS) is a heterogeneous developmental disorder where 70% of clinically diagnosed patients harbor a variant in one of five CdLS associated cohesin proteins. Around 500 variants have been identified to cause CdLS, however only eight different alterations have been identified in the RAD21 gene, encoding the RAD21 cohesin complex component protein that constitute the link between SMC1A and SMC3 within the cohesin ring. We report a 15-month-old boy presenting with developmental delay, distinct CdLS-like facial features, gastrointestinal reflux in early infancy, testis retention, prominent digit pads and diaphragmatic hernia. Exome sequencing revealed a novel RAD21 variant, c.1774_1776del, p.(Gln592del), suggestive of CdLS type 4. Segregation analysis of the two healthy parents confirmed the variant as de novo and bioinformatic analysis predicted the variant as disease-causing. Assessment by in silico structural model predicted that the p.Gln592del variant results in a discontinued contact between RAD21-Lys591 and the SMC1A residues Glu1191 and Glu1192, causing changes in the RAD21-SMC1A interface. In conclusion, we report a patient that expands the clinical description of CdLS type 4 and presents with a novel RAD21 p.(Glu592del) variant that causes a disturbed RAD21-SMC1A interface according to in silco structural modeling.
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- Hellman, Urban, et al.
(författare)
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A genealogical and clinical study of the phenotypical variation within the Swedish transthyretin His88Arg (p. His108Arg) amyloidosis family
- 2015
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Ingår i: European Journal of Medical Genetics. - : Elsevier BV. - 1769-7212 .- 1878-0849. ; 58:4, s. 211-215
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Tidskriftsartikel (refereegranskat)abstract
- In 2005 we reported the first case of transthyretin His88Arg (p. His108Arg) amyloidosis, a mutation characterised by cardiomyopathy. Six additional gene carriers of whom five have clinical symptoms of disease have now been identified in Sweden, and we have been able to identify a possible founder and to characterise the Swedish phenotype of the transthyretin (TTR) His88Arg mutation. Genealogical studies of church records were used to identify the individuals with the disease and their families. Routine clinical investigations of neurological and heart manifestation of the disease were utilised. We found that genealogically all seven individuals were related and originated from the same region in Sweden. Amyloid deposits were demonstrated in biopsies and the TTR His88Arg mutation was identified in all patients. Patients had a late onset disease (similar to 50 years of age) and all exhibited a severe amyloid cardiomyopathy. A pronounced peripheral axonal neuropathy was with certainty demonstrated in one patient only, who also was operated for a magnetic resonance confirmed spinal stenosis, however, without any effect on his neurological symptoms. Five of the patients had carpal tunnel syndrome. The first reported case is now deceased from cardiac failure. One patient has had a sequential heart and liver transplantation. One gene carrier had no symptoms or findings of disease on latest evaluation at the age of 44. In conclusion: the Swedish TTRHis88Arg patients all have a common Swedish founder. Cardiomyopathy with heart failure, as well as carpal tunnel syndrome and spinal stenosis were early signs of disease; but peripheral neuropathy was present in one patient before symptoms of cardiomyopathy so the phenotypical presentation of this mutation is variable.
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- Middleton, Anna, et al.
(författare)
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Attitudes of publics who are unwilling to donate DNA data for research.
- 2019
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Ingår i: European Journal of Medical Genetics. - : Elsevier BV. - 1769-7212 .- 1878-0849. ; 62:5, s. 316-323
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Tidskriftsartikel (refereegranskat)abstract
- With the use of genetic technology, researchers have the potential to inform medical diagnoses and treatment in actionable ways. Accurate variant interpretation is a necessary condition for the utility of genetic technology to unfold. This relies on the ability to access large genomic datasets so that comparisons can be made between variants of interest. This can only be successful if DNA and medical data are donated by large numbers of people to 'research', including clinical, non-profit and for-profit research initiatives, in order to be accessed by scientists and clinicians worldwide. The objective of the 'Your DNA, Your Say' global survey is to explore public attitudes, values and opinions towards willingness to donate and concerns regarding the donation of one's personal data for use by others. Using a representative sample of 8967 English-speaking publics from the UK, the USA, Canada and Australia, we explore the characteristics of people who are unwilling (n = 1426) to donate their DNA and medical information, together with an exploration of their reasons. Understanding this perspective is important for making sense of the interaction between science and society. It also helps to focus engagement initiatives on the issues of concern to some publics.
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- Winberg, Johanna, et al.
(författare)
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No evidence for mosaic pathogenic copy number variations in cardiac tissue from patients with congenital heart malformations.
- 2015
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Ingår i: European Journal of Medical Genetics. - : Elsevier BV. - 1769-7212 .- 1878-0849. ; 58:3, s. 129-133
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate if pathogenic copy number variations (CNVs) are present in mosaic form in patients with congenital heart malformations. We have collected cardiac tissue and blood samples from 23 patients with congenital heart malformations that underwent cardiac surgery and screened for mosaic gene dose alterations restricted to cardiac tissue using array comparative genomic hybridization (array CGH). We did not find evidence of CNVs in mosaic form after array CGH analysis. Pathogenic CNVs that were present in both cardiac tissue and blood were detected in 2/23 patients (9%), and in addition we found several constitutional CNVs of unclear clinical significance. This is the first study investigating mosaicism for CNVs in heart tissue compared to peripheral blood and the results do not indicate that pathogenic mosaic copy number changes are common in patients with heart malformations. Importantly, in line with previous studies, our results show that constitutional pathogenic CNVs are important factors contributing to congenital heart malformations.
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