Variations in Clinical Findings of Patients with Identical Tuberous Sclerosis Gene Mutations

Colorectal carcinogenesis involves environmental factors and genetic predispositions. Recent studies have suggested the associations between colorectal neoplasm and functional polymorphism of matrix metalloproteinases (MMPs) and cytokine genes. In this study, we analyzed polymorphisms of MMPs and tumor necrosis factor (TNF)-alpha genes, focusing on the susceptibility to colorectal neoplasm and the tumor progression. The subjects were 186 patients (95 men and 91 women) who underwent total colonoscopy, and were classified into cancer, adenoma and non-neoplasm (control) groups of 47, 72 and 67 patients, respectively. The polymorphisms at the MMP-2 ?1306C/T, MMP-3 ?1171 5A/6A, MMP-7 ?181A/G, MMP-9 ?1562C/T and TNF-alpha ?308G/A loci were analyzed. Regarding background factors, significant differences were found in the age, sex ratio and alcohol-drinking and cigarette-smoking histories in the adenoma and cancer groups, compared to those in the control group. On these factors-adjusted logistic regression analysis of polymorphisms and disease susceptibility, no significant difference was noted in the frequency of any polymorphism in the adenoma and cancer groups, compared to those in the control group. The analysis of the involvement of polymorphisms in tumor progression in the adenoma and cancer groups revealed that the odds ratio for the MMP-3 5A allele was significantly higher in the cancer group (2.74; 95% confidence interval = 1.11?6.74, P = 0.02). The polymorphisms of MMP genes and TNF-alpha genes were not associated with the susceptibility to colorectal neoplasm, but the involvement of the MMP-3 5A allele in the progression of adenoma to cancer was suggested

Dioxins and Fatty Acids in Breast Milk of Primiparas in Yonago District, Tottori Prefecture, Japan

We analyzed the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in breast milk collected 1 week after childbirth from 8 primiparas in Yonago district, Tottori Prefecture, and investigated the relationship between PCDDs or PCDFs and fatty acids in concentration, and the relationship between dioxin concentration and kind of daily foods. The mean total content of dioxins (PCDDs and PCDFs) was 0.48 pg-toxic equivalent (TEQ)/g (range 0.12?1.04 pg-TEQ/g) in breast milk, and 16.7 pg-TEQ/g-fat (range 9.6?32.7 pg-TEQ/g-fat) in total lipids of breast milk. The 8 primiparas showed a low mean dioxin concentration: the levels were lower in 6 of them and higher in 2 of them than in primiparas living in other cities in Japan. For 1 of the 2 mothers, the reason for the high level was thought to be her poor intake of vegetables in the diet. The total dioxin content was well correlated with the total lipid content ranging from 1% to 3%. Fatty acids with C16:0 and C18:1 dominated those with C12:0, C14:0, C16:1, C18: 2 and C18:0, which were commonly detected. The amount of fatty acids with C10:0, C20:1, C20:2, C20:3, C20:4, C22:5 and C22:6 was small. Gas chromatograms of these fatty acids generally showed similar distributions in breast milk of the 8 primiparas. The contents of fatty acids ranged from 17.1 to 31.3 mg/g (average 24.0 mg/g) in bulk breast milk. No clear correlation was found in concentration between PCDDs or PCDFs and specific fatty acids in breast milk

A Study on the Incidence and Comorbidities of Autism Spectrum Disorders Accompanied by Intellectual Disabilities in Yonago City, Japan

[Background] Autism spectrum disorders (ASD) with intellectual disabilities may be associated with many factors. This study focused on patients with ASD with intellectual disabilities, defined by a threshold intelligence quotient (IQ) or development quotient (DQ) of 70. We also discuss comorbidities and other factors related to ASD. [Methods] We extracted case records of patients born between April 1995 and March 2001 who lived in Yonago City, as of January 2011, and had visited the two specialist institutions for consultation regarding developmental issues. The list was further narrowed down to patients identified, as having ASD by pediatric neurologists based on Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5). We selected patients with < IQ/DQ 70 using the most recent intelligence/development test to determine comorbidities and other factors related to ASD. [Results] The data of 81 patients (59 males and 22 females) were extracted, corresponding to an incidence of 76.2 patients out of every 10,000 births. The male-to-female ratio was 2.7:1. Comorbidities and related factors of ASD were observed in 25 cases (30.9%). Eleven cases had perinatal abnormalities. Other abnormalities were observed in 17 cases, including epilepsies in 7, chromosomal abnormalities in 4, familial mental retardation in 1, and acquired brain injury in 1. [Conclusion] It is important to treat and support individuals with ASD and intellectual disabilities taking into account the characteristics and prognosis of the comorbidities and related factors

Tuberous Sclerosis 2 Gene Is Expressed at High Levels in Specific Types of Neurons in the Mouse Brain

Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by mental retardation, epilepsy and hamartomatous growth in many tissues. The gene (TSC2) encoding a tumor suppressor protein whose mutations cause TSC, has been demonstrated to be expressed at high levels in the adult and developing brain, raising the question of whether or not the TSC2 gene product has unique roles in differentiation related to cytoskeletal interactions within the central nervous system, in addition to a tumor suppressor function. To determine the expression of TSC2 in functionally distinct neuron types of the mouse brain, we carried out in situ hybridization with digoxigenin-labeled riboprobes for the detection of TSC2 mRNA. High levels of the TSC2 gene were in neurons of the pyramidal and dentate granular layer in the hippocampus, cerebellar Purkinje cells, neurons of the piriform cortex, motor neurons in the medulla and interneurons in the striatum, while intermediate levels were in cortical neurons, striatal neurons, septal neurons, thalamic neurons and neurons in the substantia nigra compacta. Thus, the high expression of the TSC2 gene has restricted distribution in specific neuronal types which are characterized by well-developed dendrites and rich in use-dependent long-term changes in synaptic efficacy. These results suggest that the function of the TSC2 gene product may be involved on a cellular basis in neuronal plasticity and relevant to mental retardation observed in TSC patients

A New X-Linked Mental Retardation Syndrome with Diplegia and Delayed Myelination

We report three boys (4, 6 and 8 years old) in a Japanese family with X-linked (XL) recessive severe mental retardation (MR), rigidospastic diplegia, mild athetotic movement of the upper limbs, delayed myelination and poor weight gain. Neurological manifestations were non-progressive. No deterioration of development, convulsion, cerebellar signs, dysarthria, pseudobulbar signs, or minor anomalies including facial dysmorphism or macro-orchidism were found. Ocular fundus was normal. The patients' mothers and one grandmother were clinically normal. Blood chemistry was within normal limits. Serum anti-human T-cell leukemia virus-I antibody titer was negative. Levels of plasma amino acids and serum very long chain fatty acids, and lysozomal enzyme activities from leukocytes were normal. Brain magnetic resonance imaging scans showed delayed myelination. Fragile X (FRAXA), fragile XE (FRAXE), proteolipid protein and L1 cell adhesion molecule (L1CAM) genes were normal. These findings were not consistent with previously reported 13 XLMR syndromes with paralysis. We conclude that this condition is a distinct and previously undescribed XLMR syndrome