Girerd B.,University Paris - Sud |
Girerd B.,Center National Of Reference Of Lhypertension Pulmonaire Severe |
Girerd B.,French Institute of Health and Medical Research |
Montani D.,University Paris - Sud |
And 23 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2010
Rationale: Activin A receptor type II-like kinase-1 (ACVRL1, also known as ALK1) mutation is a cause of hereditary hemorrhagic telangiectasia (HHT) and/or heritable pulmonary arterial hypertension (PAH). Objectives: To describe the characteristics of patients with PAH carrying an ACVRL1 mutation. Methods: We reviewed clinical, functional, and hemodynamic characteristics of 32 patients with PAH carrying an ACVRL1 mutation, corresponding to 9 patients from the French PAH Network and 23 from literature analysis. These cases were compared with 370 patients from the French PAH Network (93 with a bone morphogenetic protein receptor type 2 [BMPR2] mutation and 277 considered as idiopathic cases without identified mutation). Distribution of mutations in the ACVRL1 gene in patients with PAH was compared with the HHT Mutation Database. Measurements and Main Results: At diagnosis, ACVRL1 mutation carriers were significantly younger (21.8 ± 16.7 yr) than BMPR2 mutation carriers and noncarriers (35.7 ± 14.9 and 47.6 ± 16.3 yr, respectively; P < 0.0001). In seven of the nine patients from the French PAH Network, PAH diagnosis preceded manifestations of HHT. ACVRL1 mutation carriers had better hemodynamic status at diagnosis, but none responded to acute vasodilator challenge and they had shorter survival when compared with other patients with PAH despite similar use of specific therapies. ACVRL1 mutations in exon 10 were more frequently observed in patients with PAH, as compared with what was observed in the HHT Mutation Database (33.3 vs. 5%; P < 0.0001). Conclusions: ACVRL1 mutation carriers were characterized by a younger age at PAH diagnosis. Despite less severe initial hemodynamics and similar management, these patients had worse prognosis compared with other patients with PAH, suggesting more rapid disease progression. Source
Jobling R.K.,University of Toronto |
Assoum M.,Aix - Marseille University |
Gakh O.,Mayo Medical School |
Blaser S.,University of Toronto |
And 19 more authors.
Brain : a journal of neurology | Year: 2015
Non-progressive cerebellar ataxias are a rare group of disorders that comprise approximately 10% of static infantile encephalopathies. We report the identification of mutations in PMPCA in 17 patients from four families affected with cerebellar ataxia, including the large Lebanese family previously described with autosomal recessive cerebellar ataxia and short stature of Norman type and localized to chromosome 9q34 (OMIM #213200). All patients present with non-progressive cerebellar ataxia, and the majority have intellectual disability of variable severity. PMPCA encodes α-MPP, the alpha subunit of mitochondrial processing peptidase, the primary enzyme responsible for the maturation of the vast majority of nuclear-encoded mitochondrial proteins, which is necessary for life at the cellular level. Analysis of lymphoblastoid cells and fibroblasts from patients homozygous for the PMPCA p.Ala377Thr mutation and carriers demonstrate that the mutation impacts both the level of the alpha subunit encoded by PMPCA and the function of mitochondrial processing peptidase. In particular, this mutation impacts the maturation process of frataxin, the protein which is depleted in Friedreich ataxia. This study represents the first time that defects in PMPCA and mitochondrial processing peptidase have been described in association with a disease phenotype in humans. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: email@example.com. Source
Hyon C.,University Pierre and Marie Curie |
Marlin S.,Unite de Genetique Clinique |
Chantot-Bastaraud S.,University Pierre and Marie Curie |
Mabboux P.,University Pierre and Marie Curie |
And 6 more authors.
European Journal of Medical Genetics | Year: 2011
Submicroscopic duplications of the genomic interval deleted in Miller-Dieker syndrome (MDS) were recently identified by array-based comparative genomic hybridization (a-CGH) studies, describing new genomic disorders in the MDS locus. These rearrangements of varying size, from 59-88. kb to 4. Mb, were non-recurrent, and appear to result from diverse molecular mechanisms. Only five patients had overlapping 17p13.3 duplications including the entire MDS critical region. We describe here a 13-year-old girl with a novel microduplication of the MDS critical region, involving the PAFAH1B1 and YWHAE genes. She presented with moderate psychomotor retardation, speech delay, behavioral problems, and bilateral cleft lip and palate, a previously unreported manifestation. Initially diagnosed as having an apparently simple terminal Xq26 deletion on standard cytogenetic analysis, she was found to have an associated terminal 4.2. Mb 17p13.3 submicroscopic duplication, identified by subtelomere FISH analysis, further characterized by high-resolution array CGH, resulting from an unbalanced X;17 translocation. Phenotypic comparison with the 5 other patients previously described, revealed common phenotypic features, such as hypotonia, mild to moderate developmental delay/mental retardation, speech abnormalities, behavioral problems, recurrent infections, relatively increase of body weight, discrete facial dysmorphism including downslanting palpebral fissures, broad midface, pointed chin, contributing to further delineate this new 17p13.3 microduplication syndrome. © 2010 Elsevier Masson SAS. Source
Bennouna-Greene V.,University of Strasbourg |
Kremer S.,University of Strasbourg |
Stoetzel C.,University of Strasbourg |
Christmann D.,University of Strasbourg |
And 11 more authors.
Clinical Genetics | Year: 2011
The Bardet-Biedl syndrome (BBS) is a rare ciliopathy clinically defined by the association of retinitis pigmentosa, polydactyly, obesity, kidney disease and cognitive impairment. The cognitive functioning, behavioral phenotype, prevalence of psychiatric diseases and memory performances of a cohort of 34 patients with BBS were evaluated and a systemic brain magnetic resonance imaging (MRI) was performed. The patients' cognitive functioning was of marked variable efficiency ranging from normal to disabling performances. Neuropsychological disorders such as slow thought process, attention difficulties and obsessive-compulsive traits were observed. Our main finding was hippocampal dysgenesis, diagnosed by MRI, found in 42.31% of the patients in this cohort. Moreover, we show that BBS proteins are expressed in the human hippocampus and in the human brain in the normal subject. Recent literature in the murine model shows that hippocampal neurogenesis, in particular in the adult mouse, requires an intact primary cilia. These results encourage us to further investigate the possible role of BBS proteins in the hippocampus and related central nervous system structures. © 2011 John Wiley & Sons A/S. Source
A case of Kabuki syndrome admitted for acute diarrhea and growth retardation in a French hospital in tropical area [Syndrome de Kabuki en milieu tropical chez un nourrisson hospitalisé pour diarrhée et stagnation pondérale]
Santiago J.,Center Hospitalier Of Mayotte |
Muszlak M.,Center Hospitalier Of Mayotte |
Goulois E.,Center Hospitalier Of Mayotte |
Ranaivoarivony V.,Center Hospitalier Of Mayotte |
And 3 more authors.
Archives de Pediatrie | Year: 2010
The authors report on a 6-month-old girl with Kabuki syndrome, admitted for acute diarrhoea and growth retardation at the Mayotte hospital. From this case, they try to explain the way of understanding and management in front of dysmorphic features. © 2010 Elsevier Masson SAS. Source