Novel variant of FBN2 in a patient with congenital contractual arachnodactyly.

Congenital contractual arachnodactyly (CCA) is a genetic connective tissue disorder that is characterized by arachnodactyly, kyphoscoliosis, marfanoid habitus, and crumpled ears. We report a case of a boy with suspected Marfan syndrome. Genetic analysis revealed c.

In vitro functional analysis of four variants of human asparagine synthetase.

The loss-of-function variants of the human asparagine synthetase (ASNS) gene cause asparagine synthetase deficiency (ASNSD). Diagnosis of ASNSD requires genetic tests because a specific biochemical diagnostic for ASNSD is not available. There are a few reports describing the functional evaluation of ASNS variants.

Japanese patients with mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency: functional analysis of five novel mutations.

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) deficiency is a metabolic disorder caused by mutations in the gene. The present study describes the identification of four cases of HMGCS2 deficiency in Japan. Hepatomegaly and severe metabolic acidosis were observed in all cases.

Maternal exposure to methylmercury causes an impairment in ependymal cilia motility in the third ventricle and dilation of lateral ventricles in mice offspring.

Background: Although maternal MeHg-exposure causes hydrocephalus in the offspring of mice, its pathogenesis has not been fully explained. In the present study, we examined the issue of how maternal MeHg-exposure in mice affects ependymal ciliary movement in the offspring and whether the lateral ventricles in offspring show dilation.

Methods: Pregnant mice were given drinking water containing 0, 10, or 20 mg/L MeHg, or a single dose of 2 mg/kg MeHg.

Deficiency of 3-hydroxybutyrate dehydrogenase (BDH1) in mice causes low ketone body levels and fatty liver during fasting.

d-3-Hydroxy-n-butyrate dehydrogenase (BDH1; EC 1.1.1.

Novel mutations in a patient with mitochondrial trifunctional protein deficiency.

We encountered a patient with mitochondrial trifunctional protein deficiency in whom the corresponding mutations were not identified by a DNA panel for newborn screening for targeted diseases. After diagnosis confirmation by an enzyme assay and immunoblotting using the autopsied liver, the re-evaluation of the panel data indicated a heterozygous deletion of exons 6-9 that was later confirmed at the genomic level. cDNA analysis also identified exonization of the 5' region of intron 9 caused by a deep intronic mutation, c.

Haploinsufficiency of A20 with a novel mutation of deletion of exons 2-3 of .

Objectives: Haploinsufficiency of A20 (HA20) due to loss-of-function mutations of leads to an autoinflammatory disease. These mutations produce a premature termination codon in most cases of HA20. However, exon deletion has not been reported.

A rare variant (p.G991A) identified in a patient with ketotic hypoglycemia.

We describe the case of a 4-year-old boy who suffered from frequent ketotic hypoglycemia (KH) but did not have hepatomegaly or elevated liver enzyme levels. However, the patient was found to have a rare variant in the gene. To detect the underlying disease in this case, we performed a gene panel analysis covering 59 genes that are involved in fatty acid oxidation, ketone body metabolism and transport, and glycogen storage diseases.

Genetic and genomic basis of the mismatch repair system involved in Lynch syndrome.

Lynch syndrome is a cancer-predisposing syndrome inherited in an autosomal-dominant manner, wherein colon cancer and endometrial cancer develop frequently in the family, it results from a loss-of-function mutation in one of four different genes (MLH1, MSH2, MSH6, and PMS2) encoding mismatch repair proteins. Being located immediately upstream of the MSH2 gene, EPCAM abnormalities can affect MSH2 and cause Lynch syndrome. Mismatch repair proteins are involved in repairing of incorrect pairing (point mutations and deletion/insertion of simple repetitive sequences, so-called microsatellites) that can arise during DNA replication.

Identification of Homozygous Somatic DICER1 Mutation in Pleuropulmonary Blastoma.

Pleuropulmonary blastoma (PPB) is a rare, progressive, and aggressive malignant intrathoracic tumor observed during childhood. Mutations in the DICER1 gene have been considered a major etiologic factor of PPB and cause a variety of tumor types in children and young adults. We present a 3-year-old boy with type II PPB.

Intronic antisense Alu elements have a negative splicing effect on the inclusion of adjacent downstream exons.

Alu elements occupy 10% of the human genome. However, although they contribute to genomic and transcriptomic diversity, their function is still not fully understood. We hypothesized that intronic Alu elements may contribute to alternative splicing.

Immunodeficiency in Two Female Patients with Incontinentia Pigmenti with Heterozygous NEMO Mutation Diagnosed by LPS Unresponsiveness.

Purpose: Anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) is caused by mutations in the NF-κB essential modulator (NEMO) or NF-κB inhibitor, alpha (IKBA) genes. A heterozygous NEMO mutation causes incontinentia pigmenti (IP) in females, while a hemizygous hypomorphic mutation of NEMO causes EDA-ID in males. In general, immunodeficiency is not shown in IP patients.

Heterozygous carriers of succinyl-CoA:3-oxoacid CoA transferase deficiency can develop severe ketoacidosis.

Succinyl-CoA:3-oxoacid CoA transferase (SCOT, gene symbol OXCT1) deficiency is an autosomal recessive disorder in ketone body utilization that results in severe recurrent ketoacidotic episodes in infancy, including neonatal periods. More than 30 patients with this disorder have been reported and to our knowledge, their heterozygous parents and siblings have had no apparent ketoacidotic episodes. Over 5 years (2008-2012), we investigated several patients that presented with severe ketoacidosis and identified a heterozygous OXCT1 mutation in four of these cases (Case1 p.

A novel mutation (c.121‑13T>A) in the polypyrimidine tract of the splice acceptor site of intron 2 causes exon 3 skipping in mitochondrial acetoacetyl-CoA thiolase gene.

Mitochondrial acetoacetyl-CoA thiolase (T2) (gene symbol: ACAT1) deficiency is an autosomal recessive disorder affecting isoleucine catabolism and ketone body utilization. In this study, mutational analysis of an Indian T2-deficient patient revealed a homozygous mutation (c.121‑13T>A) located at the polypyrimidine tract of the splice acceptor site of intron 2, and exon 3 skipping was identified by cDNA analysis using cycloheximide.

Single-nucleotide substitution T to A in the polypyrimidine stretch at the splice acceptor site of intron 9 causes exon 10 skipping in the gene.

Background: β-ketothiolase (T2, gene symbol ) deficiency is an autosomal recessive disorder, affecting isoleucine and ketone body metabolism. We encountered a patient (GK03) with T2 deficiency whose T2 mRNA level was <10% of the control, but in whom a previous routine cDNA analysis had failed to find any mutations. Genomic PCR-direct sequencing showed homozygosity for c.

Clinical and Mutational Characterizations of Ten Indian Patients with Beta-Ketothiolase Deficiency.

Beta-ketothiolase deficiency (mitochondrial acetoacetyl-CoA thiolase (T2) deficiency) is an inherited disease of isoleucine catabolism and ketone body utilization caused by ACAT1 mutations. We identified ten Indian patients who manifested with ketoacidotic episodes of variable severity. The patients showed increased urinary excretion of isoleucine-catabolic intermediates: 2-methyl-3-hydroxybutyrate, 2-methylacetoacetate, and tiglylglycine.

Exon 10 skipping in ACAT1 caused by a novel c.949G>A mutation located at an exonic splice enhancer site.

Beta-ketothiolase deficiency, also known as mitochondrial acetoacetyl-CoA thiolase (T2) deficiency, is an autosomal recessive disease caused by mutations in the acetyl‑CoA acetyltransferase 1 (ACAT1) gene. A German T2‑deficient patient that developed a severe ketoacidotic episode at the age of 11 months, was revealed to be a compound heterozygote of a previously reported null mutation, c.472A>G (p.

DNA-RNA hybrid formation mediates RNAi-directed heterochromatin formation.

Certain noncoding RNAs (ncRNAs) implicated in the regulation of chromatin structure associate with chromatin. During the formation of RNAi-directed heterochromatin in fission yeast, ncRNAs transcribed from heterochromatin are thought to recruit the RNAi machinery to chromatin for the formation of heterochromatin; however, the molecular details of this association are not clear. Here, using RNA immunoprecipitation assay, we showed that the heterochromatic ncRNA was associated with chromatin via the formation of a DNA-RNA hybrid and bound to the RNA-induced transcriptional silencing (RITS) complex.

A specific CpG site demethylation in the human interleukin 2 gene promoter is an epigenetic memory.

DNA demethylation plays a critical role in transcriptional regulation in differentiated somatic cells. However, there is no experimental evidence that CpG methylation in a small region of a genome restricts gene expression. Here, we show that the anti-CD3repsilon/CD28 antibody stimulation of human CD4+ T cells induces IL2 expression following epigenetic changes, including active demethylation of a specific CpG site, recruitment of Oct-1, and changes in histone modifications.