Leshinsky-Silver E.,Wolfson Medical Center |
Leshinsky-Silver E.,Mitochondrial Disease Center |
Leshinsky-Silver E.,Tel Aviv University |
Malinger G.,Tel Aviv University |
And 18 more authors.
European Journal of Human Genetics | Year: 2011
Aicardi-Goutiéres syndrome (AGS) is a genetic neurodegenerative disorder with clinical symptoms mimicking a congenital viral infection. Five causative genes have been described: three prime repair exonuclease1 (TREX1), ribonucleases H2A, B and C, and most recently SAM domain and HD domain 1 (SAMHD1). We performed a detailed clinical and molecular characterization of a family with autosomal recessive neurodegenerative disorder showing white matter destruction and calcifications, presenting in utero and associated with multiple mtDNA deletions. A muscle biopsy was normal and did not show any evidence of respiratory chain dysfunction. Southern blot analysis of tissue from a living child and affected fetuses demonstrated multiple mtDNA deletions. Molecular analysis of genes involved in mtDNA synthesis and maintenance (POLGα, POLGΒ, Twinkle, ANT1, TK2, SUCLA1 and DGOUK) revealed normal sequences. Sequencing of TREX1 and ribonucleases H2A, B and C failed to reveal any mutations. Whole-genome homozygosity mapping revealed a candidate region containing the SAMHD1 gene. Sequencing of the gene in the affected child and two affected fetuses revealed a large deletion (9 kb), spanning the promoter, exon1 and intron 1. The parents were found to be heterozygous for this deletion. The identification of a homozygous large deletion in the SAMHD1 gene causing atypical AGS with multiple mtDNA deletions may add information regarding the involvement of mitochondria in self-activation of innate immunity by cell intrinsic components. © 2011 Macmillan Publishers Limited All rights reserved. Source
Borrell A.,Maternal Fetal Medicine |
Borrell A.,Prenatal Diagnosis Unit |
Santolaya-Forgas J.,The New School |
Horbaczewski C.,Maternal Fetal Medicine |
And 3 more authors.
Prenatal Diagnosis | Year: 2011
Objective: To determine the ability to assess the fetal anatomy and ultrasound screening markers using three-dimensional (3D) volumes acquired during the 11th to 13th week scan, in relation to whether a fetal profile could be used as a starting section. Methods: Post hoc analysis of 3D ultrasound volumes acquired at 11 to 13weeks in 223 pregnancies was performed to identify the appropriate sections for evaluation of three screening markers and ten fetal anatomy landmarks. When possible, the fetal profile was used as the starting section for volume acquisition. Results: When the fetal profile was used, satisfactory images for assessment were obtained in 90% of cases for nuchal translucency and 72% for the nasal bone, whereas successful evaluation of the ten anatomical landmarks ranged from 0 to 99%. In alternative starting sections, the corresponding success rates were 65%, 48%, and 0-95%. Conclusion: Although performance of post hoc analysis of 3D volumes is best when carried out from a profile starting section and quicker than two-dimensional analysis, it appears to be not ready for clinical use because nuchal translucency could not be examined in 10% of the fetuses. © 2011 John Wiley & Sons, Ltd.. Source
Micale L.,Laboratory of Medical Genetics |
Turturo M.G.,Laboratory of Medical Genetics |
Fusco C.,Laboratory of Medical Genetics |
Fusco C.,University of Foggia |
And 8 more authors.
European Journal of Human Genetics | Year: 2010
Supravalvular aortic stenosis (SVAS) is a congenital narrowing of the ascending aorta, which can occur sporadically as an autosomal dominant condition or as one component of the Williams-Beuren syndrome, a complex developmental genomic disorder associated with cardiovascular, neurobehavioral, craniofacial, and metabolic abnormalities, caused by a microdeletion at 7q11.23. We report the identification of seven novel mutations within the elastin gene in 31 familial and sporadic cases of nonsyndromic SVAS. Five are frameshift mutations within the coding region of the ELN gene that result in premature stop codons (PTCs); the other two mutations abolish the donor splice site of introns 3 and 28, respectively, and are predicted to alter splicing efficiency resulting in the generation of a PTC within the same introns of the gene. In vitro analysis using minigenes and cycloheximide showed that some selected frameshift mutant alleles are substrates of nonsense-mediated mRNA decay (NMD), confirming that the functional haploinsufficiency of the ELN gene is the main pathomechanism underlying SVAS. Interestingly, molecular analysis on patient fibroblasts showed that the c.20445GC mutant allele encodes for an aberrant shorter form of the elastin polypeptide that may hamper the normal assembly of elastin fibers in a dominant-negative manner. © 2010 Macmillan Publishers Limited All rights reserved. Source
Salvador J.,Public Health Agency of Barcelona |
Salvador J.,CIBER ISCIII |
Arigita M.,Prenatal Diagnosis Unit |
Carreras E.,Hospital Vall DHebron |
And 2 more authors.
Prenatal Diagnosis | Year: 2011
Objectives: To assess the prenatal ultrasound detection rates (DR) of neural tube defects (NTDs) and its evolution over the 1992 to 2006 period in the pregnant population of the city of Barcelona. Methods: Data on the population-based register of birth defects were used to assess the evolution of the prenatal DR for isolated NTD, including anencephaly, spina bifida and encephalocele by trimester of gestation. Results: In the register, 127 isolated NTD cases, including 71 anencephalic fetuses, 49 spina bifidas and 7 encephaloceles were noted. Overall, prenatal ultrasound DR for isolated NTD was 94%. All fetuses with anencephaly or encephalocele were prenatally detected (100% DR), whereas DR for spina bifida was 84%, with no apparent variation over the observation period. An important increase in first trimester DRs was observed for anencephaly, rising from 16% in the first years of the study (1992-1996) to 71% in the last years (2002-2006). Conclusion: A high DR (94%) for isolated NTD was observed in the city of Barcelona. The single significant change across the study period was an increase in the first trimester DR for anencephaly (from 16% to 71%). © 2011 John Wiley & Sons, Ltd. Source
Robles Fradejas M.,Prenatal Diagnosis Unit |
Gonzalo Garcia I.,Prenatal Diagnosis Unit |
De las Casas Quispe A.C.,Prenatal Diagnosis Unit |
Martin Garcia A.,Prenatal Diagnosis Unit |
And 2 more authors.
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2016
Objectives: To describe a case diagnosed with intracranial teratoma in week 32 of gestation, as well as review of the literature in order to discern the appropriate treatment method and general prognosis of this anomaly. Methods: A literature search was performed on the prenatal diagnosis of congenital intracranial teratomas in MEDLINE, EMBASE, Cochrane library data bases. Evaluated in this review are parameters such as time of prenatal diagnosis, associated pathology, size of tumors, method of terminating pregnancy, perinatal outcome and histological study of the tumor. Results: A total of 49 cases were found, of which 12 were finished gestation, 28 cesarean section was performed and only nine had vaginal delivery. All died in the neonatal period except in three cases with intrauterine death after diagnosis. Conclusion: As the incidence of intracranial immature teratomas is very low and the prognosis is poor, their prenatal diagnosis and obstetric management present a great challenge for the planning of a follow-up and treatment of the disease in accordance with the preferences of the parents. © 2016 Informa UK Limited, trading as Taylor & Francis Group. Source