Familial schwannomatosis carrying variant p.R340X with brain tumor: A case report.

Schwannomatosis (SWN) is a rare genetic condition characterized by the risk of developing multiple benign peripheral nerve sheath tumors; however, the risk of developing malignant tumors in patients with SWN remains unclear. This study described the case of a 57-year-old Japanese man diagnosed with SWN whose older brother also had SWN. Whole-exome sequencing identified a heterozygous mutation [c.

A Patient with Kabuki Syndrome Mutation Presenting with Very Severe Aplastic Anemia.

Kabuki syndrome (KS) is a rare congenital disorder commonly complicated by humoral immunodeficiency. Patients with KS present with mutation in the histone-lysine N-methyltransferase 2D (KMT2D) gene. Although various KMT2D mutations are often identified in lymphoma and leukemia, those encountered in aplastic anemia (AA) are limited.

Comprehensive analysis for detecting radiation-specific molecules expressed during radiation-induced rat thyroid carcinogenesis.

Although the association between radiation exposure and thyroid carcinogenesis is epidemiologically evident, 'true' radiation-induced cancers cannot be identified from biological evidence of radiation-associated cases. To assess the individual risk for thyroid cancer due to radiation exposure, we aimed to identify biomarkers that are specifically altered during thyroid carcinogenesis after irradiation in a time-dependent manner in an animal model. Thyroid glands were obtained from rats (n = 175) at 6-16 months after local X-ray (0.

Progressive Massive Splenomegaly in an Adult Patient with Kabuki Syndrome Complicated with Immune Thrombocytopenic Purpura.

Kabuki syndrome is characterized by multiple systemic anomalies and intellectual disability. It is complicated with immunodeficiencies and autoimmune disorders. The syndrome is caused by a mutation in the KMT2D gene.

mRNA Expression as a Novel Prognostic Marker in Papillary Thyroid Carcinomas.

Telomerase reverse transcriptase () promoter mutations have been found in a subset of papillary thyroid carcinomas (PTCs) and are associated with tumor aggressiveness and worse prognosis. However, little is known about the status of mRNA expression and its relationship between promoter mutations and clinicopathological features. We analyzed 159 PTC samples for promoter mutations using direct DNA sequencing.

Ultra-sensitive droplet digital PCR for detecting a low-prevalence somatic GNAQ mutation in Sturge-Weber syndrome.

Droplet digital PCR (ddPCR), a method for measuring target nucleic acid sequence quantity, is useful for determining somatic mutation rates using TaqMan probes. In this study, the detection limit of copy numbers of test DNA by ddPCR was determined based on Poisson distribution. Peptide nucleic acid (PNA), which strongly hybridises to target lesions, can inhibit target amplification by PCR.

Heterozygous mutations in cyclic AMP phosphodiesterase-4D (PDE4D) and protein kinase A (PKA) provide new insights into the molecular pathology of acrodysostosis.

Acrodysostosis without hormone resistance is a rare skeletal disorder characterized by brachydactyly, nasal hypoplasia, mental retardation and occasionally developmental delay. Recently, loss-of-function mutations in the gene encoding cAMP-hydrolyzing phosphodiesterase-4D (PDE4D) have been reported to cause this rare condition but the pathomechanism has not been fully elucidated. To understand the pathogenetic mechanism of PDE4D mutations, we conducted 3D modeling studies to predict changes in the binding efficacy of cAMP to the catalytic pocket in PDE4D mutants.

Transforming growth factor beta1 (TGFβ1) polymorphisms and breast cancer risk.

Transforming growth factor β1 (TGFβ1) is suggested to be involved in the pathogenesis of and in complications with breast cancer (BC). Polymorphisms in TGFβ1 gene (TGFβ1) have been suggested by many investigators to have a role in susceptibility to BC; however, many discordant data have been reported. Considering the role of ethnic variations, we performed an association study between TGFβ1 polymorphisms and BC among Iranian women.

MLL2 and KDM6A mutations in patients with Kabuki syndrome.

Kabuki syndrome is a congenital anomaly syndrome characterized by developmental delay, intellectual disability, specific facial features including long palpebral fissures and ectropion of the lateral third of the lower eyelids, prominent digit pads, and skeletal and visceral abnormalities. Mutations in MLL2 and KDM6A cause Kabuki syndrome. We screened 81 individuals with Kabuki syndrome for mutations in these genes by conventional methods (n = 58) and/or targeted resequencing (n = 45) or whole exome sequencing (n = 5).

Coding region polymorphisms in the indoleamine 2,3-dioxygenase (INDO) gene and recurrent spontaneous abortion.

Indoleamine 2,3-dioxygenase (INDO) catalyzes degradation of the indole ring of indoleamines and locally depletes tryptophan. INDO expression suppresses T cell proliferation and activation. Genetic variation in the INDO gene may contribute to the variable INDO enzyme expression, activity and severity of some diseases.

Developmentally dynamic changes of DNA methylation in the mouse Snurf/Snrpn gene.

The mouse Snurf/Snrpn gene has two differentially methylated regions (DMRs), the maternally methylated region at the 5' end (DMR1) and the paternally methylated region at the 3' end (DMR2). DMR1, a region that includes the Snrpn promoter and the entire intron 1, has been thought to be a germline DMR, which inherits the parental-specific methylation profile from the gametes. DMR1 is not only associated with imprinted Snrpn expression, but implicated in imprinting control of other genes in the region.

Mutations in CD96, a member of the immunoglobulin superfamily, cause a form of the C (Opitz trigonocephaly) syndrome.

The C syndrome is characterized by trigonocephaly and associated anomalies, such as unusual facies, psychomotor retardation, redundant skin, joint and limb abnormalities, and visceral anomalies. In an individual with the C syndrome who harbors a balanced chromosomal translocation, t(3;18)(q13.13;q12.

Role of DNA methylation and histone H3 lysine 27 methylation in tissue-specific imprinting of mouse Grb10.

Mouse Grb10 is a tissue-specific imprinted gene with promoter-specific expression. In most tissues, Grb10 is expressed exclusively from the major-type promoter of the maternal allele, whereas in the brain, it is expressed predominantly from the brain type promoter of the paternal allele. Such reciprocally imprinted expression in the brain and other tissues is thought to be regulated by DNA methylation and the Polycomb group (PcG) protein Eed.

A -16C>T substitution in the 5' UTR of the puratrophin-1 gene is prevalent in autosomal dominant cerebellar ataxia in Nagano.

The molecular bases of autosomal dominant cerebellar ataxia (ADCA) have been increasingly elucidated, but 17-50% of ADCA families still remain genetically undefined in Japan. In this study we investigated 67 genetically undefined ADCA families from the Nagano prefecture, and found that 63 patients from 51 families possessed the -16C>T change in the puratrophin-1 gene, which was recently found to be pathogenic for 16q22-linked ADCA. Most patients shared a common haplotype around the puratrophin-1 gene.

BAC array CGH reveals genomic aberrations in idiopathic mental retardation.

Array using 2,173 BAC clones covering the whole human genome has been constructed. All clones spotted were confirmed to show a unique signal at the predicted chromosomal location by FISH analysis in our laboratory. A total of 30 individuals with idiopathic mental retardation (MR) were analyzed by comparative genomic hybridization using this array.

Lack of association between the TGF-beta1 gene polymorphisms and recurrent spontaneous abortion.

Transforming growth factor-beta1 (TGF-beta1) is produced by T regulatory lymphocytes (Treg), which play an important role in the physiology of pregnancy. Several polymorphisms of the TGF-beta1 gene (TGFB1) have been reported, some with an important correlation with TGF-beta1 production and disease severity. We performed an association study between TGFB1 polymorphisms and recurrent spontaneous abortion (RSA).

Neuron-specific relaxation of Igf2r imprinting is associated with neuron-specific histone modifications and lack of its antisense transcript Air.

The mouse insulin-like growth factor II receptor (Igf2r) gene and its antisense transcript Air are reciprocally imprinted in most tissues, but in the brain, Igf2r is biallelically expressed despite the imprinted Air expression. To investigate the molecular mechanisms of such brain-specific relaxation of Igf2r imprinting, we analyzed its expression and epigenetic modifications in neurons, glial cells and fibroblasts by the use of primary cortical cell cultures. In glial cells and fibroblasts, Igf2r was maternally expressed and Air was paternally expressed, whereas in the primary cultured neurons, Igf2r was biallelically expressed and Air was not expressed.

A monozygotic twin pregnancy discordant for acardia and X-inactivation pattern.

Monochorionic, diamniotic twins discordant for acardia are reported. A 775 g acardius was dead, generally hydropic and severely malformed, while the other twin with a weight of 1314 g was phenotypically normal. Both twins had a normal 46 XX karyotype.

A monozygotic conjoined twin pregnancy discordant for laterality of cleft lip.

Conjoined twins discordant for phenotype of cleft lip are reported. One had right-sided cleft lip, while the co-twin had left-sided cleft lip. Both twins had a normal 46,XY karyotype.

Complex low-copy repeats associated with a common polymorphic inversion at human chromosome 8p23.

To characterize a submicroscopic, common 8p23 polymorphic inversion, we constructed a complete BAC/PAC-based physical map covering the entire 4.7-Mb inversion and its flanking regions. Two low-copy repeats (LCRs), REPD (approximately 1.