Search results for "Marfan Syndrome"
showing 10 items of 23 documents
Mutations in SKI in Shprintzen-Goldberg syndrome lead to attenuated TGF-β responses through SKI stabilization.
2020
ABSTRACTShprintzen-Goldberg syndrome (SGS) is a multisystemic connective tissue disorder, with considerable clinical overlap with Marfan and Loeys-Dietz syndromes. These syndromes have commonly been associated with enhanced TGF-β signaling. In SGS patients, heterozygous point mutations have been mapped to the transcriptional corepressor SKI, which is a negative regulator of TGF-β signaling that is rapidly degraded upon ligand stimulation. The molecular consequences of these mutations, however, are not understood. Here we use a combination of structural biology, genome editing and biochemistry to show that SGS mutations in SKI abolish its binding to phosphorylated SMAD2 and SMAD3. This resul…
Native Mitral Valve Endocarditis Caused by Neisseria elongata subsp. nitroreducens in a Patient with Marfan Syndrome: First Case in Italy and Review …
2016
Neisseria elongata(NE) is an aerobic Gram-negative organism that constitutes part of the commensal human normal oropharyngeal flora. Although previously considered not to be pathogenic, it has been recognized as an occasional cause of significant infections in humans. We report here the first case in Italy of infective endocarditis of a native prolapsing mitral valve in a patient with Marfan syndrome, caused by NE subspeciesnitroreducenswhich has been rarely isolated from clinical specimens. The culprit organism has been confirmed by mass spectrometry directly from the positive blood culture, as previously reported. The amplified gene has been deposited in GenBank under accession number KT5…
WES/WGS Reporting of Mutations from Cardiovascular "Actionable" Genes in Clinical Practice: A Key Role for UMD Knowledgebases in the Era of Big Datab…
2016
International audience; High-throughput next-generation sequencing such as whole-exome and whole-genome sequencing are being rapidly integrated into clinical practice. The use of these techniques leads to the identification of secondary variants for which decisions about the reporting or not to the patient need to be made. The American College of Medical Genetics and Genomics recently published recommendations for the reporting of these variants in clinical practice for 56 "actionable" genes. Among these, seven are involved in Marfan Syndrome And Related Disorders (MSARD) resulting from mutations of the FBN1, TGFBR1 and 2, ACTA2, SMAD3, MYH11 and MYLK genes. Here, we show that mutations col…
Lumbar spine mobility in Marfan syndrome
1993
Low back pain symptoms and lumbar spine mobility were assessed by questionnaires and by clinical and radiological measurements in 32 patients with Marfan syndrome. Frequently occurring low back pain was reported by 19% of the patients, but the disability was slight in all of them. Flexion and extension mobility of the lumbar spine (L1-S1) assessed from radiographs was 59.9 degrees and 13.2 degrees, respectively. Mean lumbar angular mobility between flexion and extension radiographs was 7.4 degrees at L1-2, 13.2 degrees at L2-3, 16.0 degrees at L3-4, 19.3 degrees at L4-5 and 18.3 degrees at L5-S1. No correlation was found between the manual assessment of lumbar segmental instability and radi…
Incidence of cardiovascular events and risk markers in a prospective study of children diagnosed with Marfan syndrome
2018
Little is known about the incidence of cardiovascular events (CVEs) and their associated risk markers in children with Marfan syndrome (MFS).To assess the incidence of CVEs and determine risk markers in a cohort diagnosed with Marfan syndrome during childhood and followed for several years.From a French multicentre nationwide database, 462 patients with MFS diagnosed during childhood were included prospectively. Patients' files were screened for a period of 20 years (1993-2013). CVEs (e.g. death, aortic dissection, cardiac valve or aortic root surgery) were assessed during the prospective follow-up.Median (interquartile range) age at the end of follow-up was 17.2 (11.1-21.3) years. CVEs wer…
Prospective risk stratification of sudden cardiac death in Marfan's syndrome.
2013
Marfan syndrome (MFS) is a variable, autosomal-dominant disorder of the connective tissue. In MFS serious ventricular arrhythmias and sudden cardiac death (SCD) can occur. The aim of this prospective study was to reveal underlying risk factors and to prospectively investigate the association between MFS and SCD in a long-term follow-up.77 patients with MFS were included. At baseline serum N-terminal pro-brain natriuretic peptide (NT-proBNP), transthoracic echocardiogram, 12-lead resting ECG, signal-averaged ECG (SAECG) and a 24-h Holter ECG with time- and frequency domain analyses were performed. The primary composite endpoint was defined as SCD, ventricular tachycardia (VT), ventricular fi…
De novo 15q21.1q21.2 deletion identified through FBN1 MLPA and refined by 244K array-CGH in a female teenager with incomplete Marfan syndrome
2010
International audience; Interstitial deletions involving the 15q21.1 band are very rare. Only 4 of these cases have been studied using molecular cytogenetic techniques in order to confirm the deletion of the whole FBN1 gene. The presence of clinical features of the Marfan syndrome (MFS) spectrum associated with mental retardation has been described in only 2/4 patients. Here we report on a 16-year-old female referred for suspicion of MFS (positive thumb and wrist sign, scoliosis, joint hyperlaxity, high-arched palate with dental crowding, dysmorphism, mitral insufficiency with dystrophic valve, striae). She had therefore 3 minor criteria according to the Ghent nosology. She also had speech …
Automatic determination of aortic compliance with cine-magnetic resonance imaging - An application of fuzzy logic theory
2002
International audience; Abstract: RATIONALE AND OBJECTIVES. Aortic compliance is defined as the relative change in aortic cross-sectional area divided by the change in arterial pressure. Magnetic resonance imaging (MRI) is a useful imaging modality for the noninvasive evaluation of aortic compliance. However, manual tracing of the aortic contour is subject to important interobserver variations. To estimate the aortic compliance from cine-MRI, a method based on fuzzy logic theory was elaborated. MATERIALS AND METHODS. Seven healthy volunteers and eight patients with Marfan syndrome were examined using an ECG gated cine-MRI sequence. The aorta was imaged in the transverse plane at the level o…
Long-Term Results After Repair of Type A Acute Aortic Dissection According to False Lumen Patency
2009
Background Late survival and freedom from retreatment on the descending aorta was evaluated after ascending aortic repair for type A acute aortic dissection (TAAAD). Methods Between March 1992 and January 2006, 189 TAAAD patients (mean age, 52 ± 11; range, 17 to 83 years) were included; of these, 58 had a patent false lumen, and 49 had Marfan syndrome. The descending aorta was evaluated postoperatively with computed tomography (CT). Late outcomes were assessed by Cox regression analysis and actuarial survival and freedom from retreatment by the Kaplan-Meier method. Mean follow-up was 88 ± 44 months. Results There were 38 (20%) late deaths. At 10 years, survival was 89.8% ± 2.1% for patients…
In-Frame Mutations in Exon 1 of SKI Cause Dominant Shprintzen-Goldberg Syndrome
2012
International audience; Shprintzen-Goldberg syndrome (SGS) is characterized by severe marfanoid habitus, intellectual disability, camptodactyly, typical facial dysmorphism, and craniosynostosis. Using family-based exome sequencing, we identified a dominantly inherited heterozygous in-frame deletion in exon 1 of SKI. Direct sequencing of SKI further identified one overlapping heterozygous in-frame deletion and ten heterozygous missense mutations affecting recurrent residues in 18 of the 19 individuals screened for SGS; these individuals included one family affected by somatic mosaicism. All mutations were located in a restricted area of exon 1, within the R-SMAD binding domain of SKI. No mut…