Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by the arrest of fetal lung formation, resulting in neonatal death due to ...acute respiratory failure and pulmonary arterial hypertension. Heterozygous single-nucleotide variants or copy-number variant (CNV) deletions involving the
gene and/or its lung-specific enhancer are found in the vast majority of ACDMPV patients. ACDMPV is often accompanied by extrapulmonary malformations, including the gastrointestinal, cardiac, or genitourinary systems. Thus far, most of the described ACDMPV patients have been diagnosed post mortem, based on histologic evaluation of the lung tissue and/or genetic testing. Here, we report a case of a prenatally detected de novo CNV deletion (~0.74 Mb) involving the
gene in a fetus with ACDMPV and hydronephrosis. Since ACDMPV is challenging to detect by ultrasound examination, the more widespread implementation of prenatal genetic testing can facilitate early diagnosis, improve appropriate genetic counselling, and further management.
KBG syndrome is a neurodevelopmental autosomal dominant disorder characterized by short stature, macrodontia, developmental delay, behavioral problems, speech delay and delayed closing of fontanels. ...Most patients with KBG syndrome are found to have a mutation in the
gene or a chromosomal rearrangement involving this gene. We hereby present clinical evaluations of 23 patients aged 4 months to 26 years manifesting clinical features of KBG syndrome. Mutation analysis in the patients was performed using panel or exome sequencing and array CGH. Besides possessing dysmorphic features typical of the KBG syndrome, nearly all patients had psychomotor hyperactivity (86%), 81% had delayed speech, 61% had poor weight gain, 56% had delayed closure of fontanel and 56% had a hoarse voice. Macrodontia and a height range of -1 SDs to -2 SDs were noted in about half of the patients; only two patients presented with short stature below -3 SDs. The fact that wide, delayed closing fontanels were observed in more than half of our patients with KBG syndrome confirms the role of the
gene in skull formation and suture fusion. This clinical feature could be key to the diagnosis of KBG syndrome, especially in young children. Hoarse voice is a previously undescribed phenotype of KBG syndrome and could further reinforce clinical diagnosis.
Congenital heart defects (CHDs) appear in 8-10 out of 1000 live born newborns and are one of the most common causes of deaths. In fetuses, the congenital heart defects are found even 3-5 times more ...often. Currently, microarray comparative genomic hybridization (array CGH) is recommended by worldwide scientific organizations as a first-line test in the prenatal diagnosis of fetuses with sonographic abnormalities, especially cardiac defects. We present the results of the application of array CGH in 484 cases with prenatally diagnosed congenital heart diseases by fetal ultrasound scanning (256 isolated CHD and 228 CHD coexisting with other malformations). We identified pathogenic aberrations and likely pathogenic genetic loci for CHD in 165 fetuses and 9 copy number variants (CNVs) of unknown clinical significance. Prenatal array-CGH is a useful method allowing the identification of all unbalanced aberrations (number and structure) with a much higher resolution than the currently applied traditional assessment techniques karyotype. Due to this ability, we identified the etiology of heart defects in 37% of cases.
The aim of this study was to determine the suitability of the comparative genomic hybridization to microarray (aCGH) technique for prenatal diagnosis, but also to assess the frequency of chromosomal ...aberrations that may lead to fetal malformations but are not included in the diagnostic report. We present the results of the aCGH in a cohort of 7400 prenatal cases, indicated for invasive testing due to ultrasound abnormalities, high-risk for serum screening, thickened nuchal translucency, family history of genetic abnormalities or congenital abnormalities, and advanced maternal age (AMA). The overall chromosomal aberration detection rate was 27.2% (2010/7400), including 71.2% (1431/2010) of numerical aberrations and 28.8% (579/2010) of structural aberrations. Additionally, the detection rate of clinically significant copy number variants (CNVs) was 6.8% (505/7400) and 0.7% (57/7400) for variants of unknown clinical significance. The detection rate of clinically significant submicroscopic CNVs was 7.9% (334/4204) for fetuses with structural anomalies, 5.4% (18/336) in AMA, 3.1% (22/713) in the group of abnormal serum screening and 6.1% (131/2147) in other indications. Using the aCGH method, it was possible to assess the frequency of pathogenic chromosomal aberrations, of likely pathogenic and of uncertain clinical significance, in the groups of cases with different indications for an invasive test.
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by the arrest of fetal lung formation, resulting in neonatal death due to ...acute respiratory failure and pulmonary arterial hypertension. Heterozygous single-nucleotide variants or copy-number variant (CNV) deletions involving the FOXF1 gene and/or its lung-specific enhancer are found in the vast majority of ACDMPV patients. ACDMPV is often accompanied by extrapulmonary malformations, including the gastrointestinal, cardiac, or genitourinary systems. Thus far, most of the described ACDMPV patients have been diagnosed post mortem, based on histologic evaluation of the lung tissue and/or genetic testing. Here, we report a case of a prenatally detected de novo CNV deletion (~0.74 Mb) involving the FOXF1 gene in a fetus with ACDMPV and hydronephrosis. Since ACDMPV is challenging to detect by ultrasound examination, the more widespread implementation of prenatal genetic testing can facilitate early diagnosis, improve appropriate genetic counselling, and further management.
The Computing Models of the LHC experiments continue to evolve from the simple hierarchical MONARC2 model towards more agile models where data is exchanged among many Tier2 and Tier3 sites, relying ...on both large scale file transfers with strategic data placement, and an increased use of remote access to object collections with caching through CMS's AAA, ATLAS' FAX and ALICE's AliEn projects, for example. The challenges presented by expanding needs for CPU, storage and network capacity as well as rapid handling of large datasets of file and object collections have pointed the way towards future more agile pervasive models that make best use of highly distributed heterogeneous resources. In this paper, we explore the use of Named Data Networking (NDN), a new Internet architecture focusing on content rather than the location of the data collections. As NDN has shown considerable promise in another data intensive field, Climate Science, we discuss the similarities and differences between the Climate and HEP use cases, along with specific issues HEP faces and will face during LHC Run2 and beyond, which NDN could address.
Advancement in networks for HEP community Newman, Harvey B; Barczyk, Artur; Mughal, Azher
Journal of physics. Conference series,
04/2010, Letnik:
219, Številka:
6
Journal Article
Recenzirano
Odprti dostop
The key role of networks has been brought into focus as a result of the worldwide-distributed computing model adopted by the four LHC experiments, as a necessary response to the unprecedented data ...volumes and computational needs of the LHC physics program. As we approach LHC startup and the era of LHC physics, the focus has increased as the experiments develop the tools and methods needed to distribute, process, access and cooperatively analyze datasets with aggregate volumes of Petabytes of simulated data even now, rising to many Petabytes of real and simulated data during the first years of LHC operation.
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