1,721,075 research outputs found
Myoclonic movement disorder associated with microdeletion of chromosome 22q111
No full textWith a prevalence of approximately 1:4000 interstitial chromosome 22q11 deletion within the DiGeorge syndrome critical region is the commonest chromosome microdeletion syndrome. The better known clinical features of this disorder are cardiac abnormalities, short stature, palatal abnormalities or velopharangeal insufficiency, renal abnormality, hypocalcaemia, psychotic symptoms, learning difficulties, and developmental delay.1 There is wide variability in this clinical spectrum and many case reports drawing attention to new clinical features have been published. Alongside the larger studies of 22q11 cohorts these have proved useful in delineating this particular syndrome. <br/
Automated comparative sequence analysis identifies mutations in 89% of NF1 patients and confirms a mutation cluster in exons 11-17 distinct from the GAP related domain4
No full textNeurofibromatosis type 1 (NF1), formerly known as Von Recklinghausen Neurofibromatosis, is a common genetic disorder affecting approximately 1 in 3000–5000 people. It is a fully penetrant autosomal dominant disorder. Strict diagnostic criteria that include café au lait spots, neurofibromas, plexiform neurofibromas, freckling in the axillary or inguinal regions, Lisch nodules (iris haematomas), optic or chiasma glioma, pseudoarthrosis, and sphenoid dysplasia define NF1. Most disease features are present in more than 90% of patients at puberty.1 Further manifestations are known to occur in this disorder, including macrocephaly, short stature, learning difficulties, scoliosis and certain malignancies.2–4 There is, however, great intra and interfamilial phenotypic variability. In addition a number of patients who have a clinical picture suspected to be NF1 do not fulfil the diagnostic criteria particularly in the younger age groups. As a consequence genetic testing would have a major impact on the diagnosis and management of these families. <br/
Development of a diagnostic service for neurofibromatosis type 1 facilitated by automated data analysis
No full textPitfalls of automated comparative sequence analysis as a single platform for routine clinical testing for NF1 (Messiaen and Wimmer)
No full textWe are grateful to the authors for pointing out the errors in assignment of the predicted effect of some of the sequence variants that we reported.1 The same sense mutations Q282Q, C680C, K1724K, and R1808R are incorrectly recorded as protein truncating in table 2. The Y489C and G629R mutations are previously reported splice mutations. The E91X sequence change is 271GT. The D176E and R873C sequence variants should have been recorded only in table 3. We apologise for these errors. However, this does not detract from the main message of our paper that all of these sequence variants were ascertained using a single method. The reported method is an accurate and efficient way of testing for sequence changes.<br/
Identification of a mutation that perturbs NF1 agene splicing using genomic DNA samples and a minigene assay
No full textNeurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disease. In recent studies on the neurofibromatosis type 1 (NF1) gene neurofibromin, splicing abnormalities were seen in 30-50% of cases when RNA taken from cell lines was analysed.1,2 Unlike mutations that alter critical amino acids or generate premature stop codons, splicing abnormalities can be very hard to predict from sequence analysis alone. Apart from the two base pairs 5' and 3' of each exon, few of the nucleotides in regions critical for splicing are absolutely conserved. As a consequence, it can be very difficult to conclude that a sequence variation found in a patient will alter splicing and so represents a pathogenic mutation
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