Search results for "MUTATION"

Elevated serum triiodothyronine and intellectual and motor disability with paroxysmal dyskinesia caused by a monocarboxylate transporter 8 gene mutat…

2008

Monocarboxylate transporter 8 (MCT8 or SLC16A2) is important for the neuronal uptake of triiodothyronine (T3) in its function as a specific and active transporter of thyroid hormones across the cell membrane, thus being essential for human brain development. We report on a German male with Allan-Herndon-Dudley syndrome presenting with severe intellectual and motor disability, paroxysmal dyskinesia combined with truncal muscular hypotonia, and peripheral muscular hypertonia at his current age of 9 years. Additionally, the patient has a lesion in the left putamen region revealed by magnetic resonance imaging and elevated serum T3 levels. The male appeared to have a hemizygous mutation (R271H)…

Studies on the induction of gene mutations in bacterial and mammalian cells by the ring-opened benzene metabolites trans,trans-muconaldehyde and tran…

1990

t,t-Muconaldehyde and t,t-muconic acid have been investigated for the induction of gene mutations in Salmonella typhimurium (reversion of the his- strains TA97, TA98, TA100, TA102, TA104 and TA1535), Escherichia coli (reversion of the trp- strain WP2 uvrA) and Chinese hamster V79 cells (acquisition of resistance toward 6-thioguanine). t,t-Muconaldehyde proved weakly mutagenic in strain TA104 in the presence and absence of NADPH-fortified postmitochondrial fraction from rat liver homogenate (S9 mix). In strains TA97, TA100 and TA102, weak positive responses were observed only in the presence of S9 mix. In strains TA98, TA1535 and WP2 uvrA, the result was negative. In V79 cells, the mutation …

Declining Prevalence of HIV-1 Drug Resistance in Antiretroviral Treatment-exposed Individuals in Western Europe

2013

HIV-1 drug resistance represents a major obstacle to infection and disease control. This retrospective study analyzes trends and determinants of resistance in antiretroviral treatment (ART)-exposed individuals across 7 countries in Europe. Of 20 323 cases, 80% carried at least one resistance mutation: these declined from 81% in 1997 to 71% in 2008. Predicted extensive 3-class resistance was rare (3.2% considering the cumulative genotype) and peaked at 4.5% in 2005, decreasing thereafter. The proportion of cases exhausting available drug options dropped from 32% in 2000 to 1% in 2008. Reduced risk of resistance over calendar years was confirmed by multivariable analysis. © 2013 The Author.

Differential modulation of CYP2E1 activity by cAMP-dependent protein kinase upon Ser129 replacement.

1998

Many toxic compounds are activated by cytochrome P450 (CYP) 2E1 to reactive metabolites, which represents a potential hazard for cellular homeostasis. Therefore knowledge about CYP2E1 regulation could be of great biological importance. It has been shown that CYP2E1 is controlled transcriptionally and post-translationally by phosphorylation. In the present study we investigated the role of serine-129 (Ser129) in the protein kinase A (PKA) recognition sequence motif Arg-Arg-Phe-Ser129. To gain further insights into the possible relevance of Ser129 for CYP2E1 function, Ser129 was replaced by alanine (Ala) or glycine (Gly) by site-directed mutations of the cDNA coding for CYP2E1. The mutant cDN…

Mild mutations in the pan neural gene prospero affect male-specific behaviour in Drosophila melanogaster

2004

0376-6357 (Print) Journal Article Research Support, Non-U.S. Gov't; The fruitfly Drosophila melanogaster is one of the most appropriate model organisms to study the genetics of behaviour. Here, we focus on prospero (pros), a key gene for the development of the nervous system which specifies multiple aspects from the early formation of the embryonic central nervous system to the formation of larval and adult sensory organs. We studied the effects on locomotion, courtship and mating behaviour of three mild pros mutations. These newly isolated pros mutations were induced after the incomplete excision of a transposable genomic element that, before excision, caused a lethal phenotype during larv…

Thrombotic complications in paroxysmal nocturnal haemoglobinuria: a literature review.

2012

Actin-related myopathy without any missense mutation in the ACTA1 gene.

2004

Actinopathies are defined by missense mutations in the ACTA1 gene coding for sarcomeric actin, of which some 70 families have, so far, been identified. Often, but not always, muscle fibers carry large patches of actin filaments. Many such patients also have nemaline myopathy, qualifying actinopathies as a subgroup of nemaline myopathies. This article concerns a then newborn, now 21/2-year-old boy, the first and single child of nonconsanguineous parents, who was born floppy, requiring immediate postnatal assisted ventilation. A quadriceps muscle biopsy revealed large patches of thin myofilaments reacting at light and electron microscopic levels with antibodies against actin but only a few s…

Control of apterous by vestigial drives indirect flight muscle development in drosophila

2003

0012-1606 (Print) Journal Article Research Support, Non-U.S. Gov't; Drosophila thoracic muscles are comprised of both direct flight muscles (DFMs) and indirect flight muscles (IFMs). The IFMs can be further subdivided into dorsolongitudinal muscles (DLMs) and dorsoventral muscles (DVMs). The correct patterning of each category of muscles requires the coordination of specific executive regulatory programs. DFM development requires key regulatory genes such as cut (ct) and apterous (ap), whereas IFM development requires vestigial (vg). Using a new vg(null) mutant, we report that a total absence of vg leads to DLM degeneration through an apoptotic process and to a total absence of DVMs in the …

Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity

2013

The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. Although little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and adverse cardiometabolic health. The only gene so far associated with pubertal height growth, LIN28B, pleiotropically influences childhood growth, puberty and cancer progression, pointing to shared underlying mechanisms. To discover genetic loci influencing pubertal height and growth and to place them in context of overall growth and maturation, we performed genome-wide association meta-analyses i…

ZBTB20 is crucial for the specification of a subset of callosal projection neurons and astrocytes in the mammalian neocortex

2021

ABSTRACT Neocortical progenitor cells generate subtypes of excitatory projection neurons in sequential order followed by the generation of astrocytes. The transcription factor zinc finger and BTB domain-containing protein 20 (ZBTB20) has been implicated in regulation of cell specification during neocortical development. Here, we show that ZBTB20 instructs the generation of a subset of callosal projections neurons in cortical layers II/III in mouse. Conditional deletion of Zbtb20 in cortical progenitors, and to a lesser degree in differentiating neurons, leads to an increase in the number of layer IV neurons at the expense of layer II/III neurons. Astrogliogenesis is also affected in the mut…