Background
Primary chronic intestinal pseudo‐obstruction (CIPO) is a rare, potentially life‐threatening disorder characterized by severely impaired gastrointestinal motility. The objective of this ...study was to examine the contribution of ACTG2, LMOD1, MYH11, and MYLK mutations in an Australasian cohort of patients with a diagnosis of primary CIPO associated with visceral myopathy.
Methods
Pediatric and adult patients with primary CIPO and suspected visceral myopathy were recruited from across Australia and New Zealand. Sanger sequencing of the genes encoding enteric gamma‐actin (ACTG2) and smooth muscle leiomodin (LMOD1) was performed on DNA from patients, and their relatives, where available. MYH11 and MYLK were screened by next‐generation sequencing.
Key results
We identified heterozygous missense variants in ACTG2 in 7 of 17 families (~41%) diagnosed with CIPO and its associated conditions. We also identified a previously unpublished missense mutation (c.443C>T, p.Arg148Leu) in one family. One case presented with megacystis‐microcolon‐intestinal hypoperistalsis syndrome in utero with subsequent termination of pregnancy at 28 weeks' gestation. All of the substitutions identified occurred at arginine residues. No likely pathogenic variants in LMOD1, MYH11, or MYLK were identified within our cohort.
Conclusions and inferences
ACTG2 mutations represent a significant underlying cause of primary CIPO with visceral myopathy and associated phenotypes in Australasian patients. Thus, ACTG2 sequencing should be considered in cases presenting with hypoperistalsis phenotypes with suspected visceral myopathy. It is likely that variants in other genes encoding enteric smooth muscle contractile proteins will contribute further to the genetic heterogeneity of hypoperistalsis phenotypes.
Primary CIPO is a rare, potentially life‐threatening disorder characterized by severely impaired gastrointestinal motility. We identified heterozygous missense variants in ACTG2 in 7 of 17 families (~41%) diagnosed with CIPO and its associated conditions. We also identified a previously unpublished missense mutation (c.443C>T, p.Arg148Leu) in one family. ACTG2 mutations account for a substantial number of both pediatric and adult cases of CIPO and thus should be screened in all patients presenting with this phenotype.
Biomedical research projects deal with data management requirements from multiple sources like funding agencies' guidelines, publisher policies, discipline best practices, and their own users' needs. ...We describe functional and quality requirements based on many years of experience implementing data management for the CRC 1002 and CRC 1190. A fully equipped data management software should improve documentation of experiments and materials, enable data storage and sharing according to the FAIR Guiding Principles while maximizing usability, information security, as well as software sustainability and reusability.
We introduce the modular web portal software menoci for data collection, experiment documentation, data publication, sharing, and preservation in biomedical research projects. Menoci modules are based on the Drupal content management system which enables lightweight deployment and setup, and creates the possibility to combine research data management with a customisable project home page or collaboration platform.
Management of research data and digital research artefacts is transforming from individual researcher or groups best practices towards project- or organisation-wide service infrastructures. To enable and support this structural transformation process, a vital ecosystem of open source software tools is needed. Menoci is a contribution to this ecosystem of research data management tools that is specifically designed to support biomedical research projects.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A profoundly deaf female infant was found to have hypoglycemia and lactic acidemia after an episode of decreased oral intake and vomiting. Electron transport chain (ETC) enzyme studies revealed a ...combination defect of complexes I, III, and IV in liver but not in skeletal muscle. This case highlights the fact that defects of the ETC are clinically highly heterogeneous and should be considered with hypoglycemia and lactic acidosis in the absence of a glycogen storage disorder. Moreover, ETC defects can occur with a biochemical profile suggestive of a fatty acid oxidation disorder. (J Pediatr 1997;130:431-6)
Abstract
Background
Primary chronic intestinal pseudo‐obstruction (CIPO) is a rare, potentially life‐threatening disorder characterized by severely impaired gastrointestinal motility. The objective ...of this study was to examine the contribution of
ACTG
2
,
LMOD
1
,
MYH
11,
and
MYLK
mutations in an Australasian cohort of patients with a diagnosis of primary CIPO associated with visceral myopathy.
Methods
Pediatric and adult patients with primary CIPO and suspected visceral myopathy were recruited from across Australia and New Zealand. Sanger sequencing of the genes encoding enteric gamma‐actin (
ACTG
2
) and smooth muscle leiomodin (
LMOD
1) was performed on
DNA
from patients, and their relatives, where available.
MYH
11
and
MYLK
were screened by next‐generation sequencing.
Key results
We identified heterozygous missense variants in
ACTG
2
in 7 of 17 families (~41%) diagnosed with CIPO and its associated conditions. We also identified a previously unpublished missense mutation (c.443C>T, p.Arg148Leu) in one family. One case presented with megacystis‐microcolon‐intestinal hypoperistalsis syndrome
in utero
with subsequent termination of pregnancy at 28 weeks' gestation. All of the substitutions identified occurred at arginine residues. No likely pathogenic variants in
LMOD
1
,
MYH
11,
or
MYLK
were identified within our cohort.
Conclusions and inferences
ACTG
2
mutations represent a significant underlying cause of primary CIPO with visceral myopathy and associated phenotypes in Australasian patients. Thus,
ACTG
2
sequencing should be considered in cases presenting with hypoperistalsis phenotypes with suspected visceral myopathy. It is likely that variants in other genes encoding enteric smooth muscle contractile proteins will contribute further to the genetic heterogeneity of hypoperistalsis phenotypes.
Leigh disease can be caused by defects of both nuclear and mitochondrially encoded genes. One mitochondrial DNA mutation, G14459A, has been associated with both respiratory chain complex I deficiency ...and Leber's hereditary optic neuropathy, with or without dystonia. Here, we report the occurrence of this mutation in 3 complex I–deficient patients from 2 separate pedigrees who presented with Leigh disease, with no evidence or family history of Leber's hereditary optic neuropathy or dystonia. Ann Neurol 2000;48:102–104
Teacher educators should be engaged in thinking about the questions they pose to teachers to promote thinking, deeper discourse and reflection on practice. Huinker and Freckmann compare two scenarios ...based on debriefing teachers after classroom observations and then provide a model for formulating well-structured questions.
Infantile spasms (IS) is the most severe and common form of epilepsy occurring in the first year of life. At least half of IS cases are idiopathic in origin, with others presumed to arise because of ...brain insult or malformation. Here, we identify a locus for IS by high-resolution mapping of 7q11.23-q21.1 interstitial deletions in patients. The breakpoints delineate a 500 kb interval within the MAGI2 gene (1.4 Mb in size) that is hemizygously disrupted in 15 of 16 participants with IS or childhood epilepsy.
Tamara, a preservice teacher, taught a lesson on fractions to a class of fourth-grade students in her field-experience practicum. The instructor of her mathematics methods course observed the lesson. ...As they met in the hallway to debrief the teaching experience, the instructor began by asking, “How do you think your lesson went?” Tamara replied, “Great. I got through my entire lesson plan.” Tamara's comment and the subsequent discussion revealed that she was focused on her actions as the teacher but not on the dynamics of instruction (Cohen and Ball 2001).
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