scholarly journals Mutations in the human SC4MOL gene encoding a methyl sterol oxidase cause psoriasiform dermatitis, microcephaly, and developmental delay

2011 ◽  
Vol 121 (3) ◽  
pp. 976-984 ◽  
Author(s):  
Miao He ◽  
Lisa E. Kratz ◽  
Joshua J. Michel ◽  
Abbe N. Vallejo ◽  
Laura Ferris ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Gene Encoding ◽  
Methyl Sterol

Sulfonylurea-insensitive permanent neonatal diabetes caused by a severe gain-of-function Tyr330His substitution in Kir6.2

2022 ◽  
Author(s):  
Conor McClenaghan ◽  
Novella Rapini ◽  
Domenico Umberto De Rose ◽  
Jian Gao ◽  
Jacob Roeglin ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Molecular Basis ◽  
Glucose Monitoring ◽  
Neonatal Diabetes ◽  
Katp Channels ◽  
Gain Of Function ◽  
Gene Encoding ◽  
Permanent Neonatal Diabetes ◽  
Mild Developmental Delay ◽  
Atp Inhibition

Background/Aims: Mutations in KCNJ11, the gene encoding the Kir6.2 subunit of pancreatic and neuronal KATP channels, are associated with a spectrum of neonatal diabetes diseases. Methods: Variant screening was used to identify cause of neonatal diabetes, and continuous glucose monitoring used to assess effectiveness of sulfonylurea treatment. Electrophysiological analysis of variant KATP channel function was used to determine molecular basis. Results: We identified a previously uncharacterized KCNJ11 mutation, c.988T>C [pTyr330His], in an Italian child diagnosed with sulfonylurea-resistant permanent neonatal diabetes and developmental delay (iDEND). Functional analysis of recombinant KATP channels reveals that this mutation causes a drastic gain-of-function, due to a reduction in ATP-inhibition. Further, we demonstrate that the Tyr330His substitution causes a significant decrease in sensitivity to the sulfonylurea, glibenclamide. Conclusions: In this subject, the KCNJ11(c.988T>C) mutation provoked neonatal diabetes, with mild developmental delay, which was insensitive to correction by sulfonylurea therapy. This is explained by the molecular loss of sulfonylurea sensitivity conferred by the Tyr330His substitution, and highlights the need for molecular analysis of such mutations.

Characterization and Bioinformatics Analysis of C-4 Sterol Methyl Oxidase from Monascus purpureus

2014 ◽  
Vol 522-524 ◽  
pp. 247-250
Author(s):  
Jiang Ning Yao ◽  
Nan Qing Liao ◽  
Hao Ming Li
Keyword(s):  
Primary Structure ◽  
Bioinformatics Analysis ◽  
Monascus Purpureus ◽  
Transmembrane Helices ◽  
Gene Encoding ◽  
Fatty Acid Hydroxylase ◽  
Comparison Results ◽  
Methyl Sterol ◽  
Alignment Analysis ◽  
Hydrophobicity Profile

A gene encoding a putative C-4 sterol methyl oxidase was obtained by screening Monascus purpureus cDNA library. Bioinformatics analysis showed that this protein has a primary structure, a hydrophobicity profile and a pattern of histidine-rich motifs which are typical of C-4 methyl sterol oxidases. The deduced C-4 sterol methyl oxidase protein of M. purpureus contained 259 amino acid, with molecular mass of 30,299Da. Sequence alignment analysis revealed that M. purpureus deduced C-4 sterol methyl oxidase was closely related to C-4 sterol methyl oxidase from Aspergillus, Penicillium and Byssochlamys, and highly homologous to aforementioned and other known C-4 sterol methyl oxidase. The deduced protein is of a membrane protein with two transmembrane helices, which belongs to the fatty acid hydroxylase superfamily. The consistency of the comparison results of the primary structure, secondary structure and physicochemical properties suggests that the dedued protein may well be C-4 sterol methyl oxidase.

scholarly journals Homozygous STXBP1 variant causes encephalopathy and gain-of-function in synaptic transmission

Brain ◽  
2019 ◽  
Vol 143 (2) ◽  
pp. 441-451 ◽  
Author(s):  
Hanna C A Lammertse ◽  
Annemiek A van Berkel ◽  
Michele Iacomino ◽  
Ruud F Toonen ◽  
Pasquale Striano ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Synaptic Transmission ◽  
Protein Stability ◽  
Developmental Delay ◽  
Fold Increase ◽  
Null Mouse ◽  
Gain Of Function ◽  
Gene Encoding ◽  
Cellular Effects ◽  
Protein Levels

Abstract Heterozygous mutations in the STXBP1 gene encoding the presynaptic protein MUNC18-1 cause STXBP1 encephalopathy, characterized by developmental delay, intellectual disability and epilepsy. Impaired mutant protein stability leading to reduced synaptic transmission is considered the main underlying pathogenetic mechanism. Here, we report the first two cases carrying a homozygous STXBP1 mutation, where their heterozygous siblings and mother are asymptomatic. Both cases were diagnosed with Lennox-Gastaut syndrome. In Munc18-1 null mouse neurons, protein stability of the disease variant (L446F) is less dramatically affected than previously observed for heterozygous disease mutants. Neurons expressing Munc18L446F showed minor changes in morphology and synapse density. However, patch clamp recordings demonstrated that L446F causes a 2-fold increase in evoked synaptic transmission. Conversely, paired pulse plasticity was reduced and recovery after stimulus trains also. Spontaneous release frequency and amplitude, the readily releasable vesicle pool and the kinetics of short-term plasticity were all normal. Hence, the homozygous L446F mutation causes a gain-of-function phenotype regarding release probability and synaptic transmission while having less impact on protein levels than previously reported (heterozygous) mutations. These data show that STXBP1 mutations produce divergent cellular effects, resulting in different clinical features, while sharing the overarching encephalopathic phenotype (developmental delay, intellectual disability and epilepsy).

Using parental questionnaires to identify developmental delay

2005 ◽  
Vol 47 (09) ◽  
pp. 646 ◽  
Author(s):  
Alan Emond ◽  
J Clare Bell ◽  
Jon Heron
Keyword(s):  
Developmental Delay

B-Vitamins, Methylenetetrahydrofolate Reductase (MTHFR) and Hypertension

2011 ◽  
Vol 81 (4) ◽  
pp. 240-244 ◽  
Author(s):  
Mary Ward ◽  
Carol P Wilson ◽  
J J Strain ◽  
Geraldine Horigan ◽  
John M. Scott ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Low Dose ◽  
Methylenetetrahydrofolate Reductase ◽  
Genetic Determinant ◽  
Gene Encoding ◽  
Homocysteine Concentration ◽  
Homozygous Mutant ◽  
B Vitamin

Hypertension is a leading risk factor for cardiovascular disease (CVD) and stroke. A common polymorphism in the gene encoding the enzyme methylenetetrahydrofolate reductase (MTHFR), previously identified as the main genetic determinant of elevated homocysteine concentration and also recognized as a risk factor for CVD, appears to be independently associated with hypertension. The B-vitamin riboflavin is required as a cofactor by MTHFR and recent evidence suggests it may have a role in modulating blood pressure, specifically in those with the homozygous mutant MTHFR 677 TT genotype. If studies confirm that this genetic predisposition to hypertension is correctable by low-dose riboflavin, the findings could have important implications for the management of hypertension given that the frequency of this polymorphism ranges from 3 to 32 % worldwide.

Identification of a single-copy gene encoding a Type I chlorophyll a/b-binding polypeptide of photosystem I in Arabidopsis thaliana

1992 ◽  
Vol 84 (4) ◽  
pp. 561-567 ◽  
Author(s):  
Poul E. Jensen ◽  
Michael Kristensen ◽  
Tine Hoff ◽  
Jan Lehmbeck ◽  
Bjarne M. Stummann ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Chlorophyll A ◽  
Photosystem I ◽  
Single Copy ◽  
Type I ◽  
Single Copy Gene ◽  
Gene Encoding ◽  
Copy Gene
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