Diabetes mellitus carrying a mutation in the mitochondrial tRNALeu(UUR) gene

Summary We screened 214 Japanese NIDDM (non-insulin-dependent) diabetic patients with a family history of diabetes for mutations in the mitochondrial tRNA^Leu(UUR) gene using polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Six patients were identified as having an A to G transition at position 3243 (3243 mutation), but no patients were detected with a T to C transition at position 3271, in the mitochondrial tRNA^Leu(UUR) gene. These two mutations were not present in 85 healthy control subjects. It was disclosed that the patients' mothers were also affected by diabetes mellitus in five of the six cases. In these six affected patients, the 3243 mutation shows variable phenotypes, such as the degree of multiple organ involvement, intrafamilial and interfamilial differences in disease characteristics, and the degree of the involvement of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) phenotype. Endocrinological examinations revealed that those diabetic patients with the 3243 mutation show not only beta-cell dysfunction, but also a defect in alpha-cell function, which is considered characteristic of diabetes with the 3243 mutation. When compared with 50 selected diabetic control subjects without the 3243 mutation, whose mothers, but not fathers, were found to have diabetes, it was established statistically that those with the 3243 mutation possess the following clinical characteristics; 1) the age of diabetes onset is lower, 2) they have lean body constitutions, and 3) they are more likely to be treated with insulin than control subjects. We suggest that diabetes with the 3243 mutation possesses phenotypes distinct from those in common forms of diabetes.Abbreviations NIDDM non-insulin-dependent diabetes mellitus - IDDM insulin-dependent diabetes mellitus - MELAS mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes - PCR polymerase chain reaction - RFLP restriction fragment length polymorphism - BMI body mass index - ICA islet cell antibody - ICSA islet cell surface antibody - GAD glutamic acid decarboxylase     

A father and son with Turcot's syndrome: Evidence for autosomal dominant inheritance

Typical Turcot's syndrome is characterized by the association of a brain glioma together with multiple colonic polyposis, in which the number of polypoid lesions is small and the association of colonic cancer occurs at a younger age than in familial adenomatous polyposis. We describe a family in which both the father and his son presented with typical Turcot's syndrome without parental consanguinity. This is the first report of a family that is considered to follow an autosomal dominant inheritance. After reviewing 25 documented cases in which the average age of death was 20.3 years old, it was learned that the major cause of death was brain tumor (76 percent) and the minor cause was colon cancer (16 percent). Patients were very young and, therefore, unlikely to have produced a child before their death. These facts seem to support the theory that Turcot's syndrome is an autosomal dominant disorder.     

Parental longevity correlates with offspring’s optimism in two cohorts of community-dwelling older subjects

Dispositional optimism and other positive personality traits have been associated with longevity. Using a familial approach, we investigated the relationship between parental longevity and offspring’s dispositional optimism among community-dwelling older subjects. Parental age of death was assessed using structured questionnaires in two different population-based samples: the Leiden Longevity Study (n = 1,252, 52.2% female, mean age 66 years, SD = 4) and the Alpha Omega Trial (n = 769, 22.8% female, mean age 69 years, SD = 6). Adult offspring’s dispositional optimism was assessed with the Life Orientation Test—Revised (LOT-R). The association between parental age of death and levels of optimism in the offspring was analysed using linear regression analysis within each sample and a meta-analysis for the overall effect. In both samples, the parental mean age of death was positively associated with optimism scores of the offspring. The association remained significant after adjustment for age, gender, living arrangement, body mass index, smoking status, education and self-rated health of the offspring. The pooled B coefficient (increase in LOT-R score per 10-year increase in parental mean age of death) was 0.30 (SE = 0.08, p < 0.001). In conclusion, parental longevity was positively associated with optimism in adult offspring, suggesting a partial linked heritability of longevity and optimism.     

Inherited catecholaminergic polymorphic ventricular tachycardia due to RYR2 mutation

We report the case of an 11‐year‐old boy who was diagnosed with catecholaminergic polymorphic ventricular tachycardia (CPVT). The patient had a medical history of three episodes of syncope. The last episode was cardiac arrest while swimming. After resuscitation using automated external defibrillator, he was placed under cerebral hypothermia, examined for long QT syndrome, and underwent insertion of implantable cardioverter defibrillator. He was subsequently discharged from hospital without any adverse sequelae. The patient was diagnosed with CPVT after detection of ryanodine receptor 2 mutation. His father also carried the same mutation, although he did not have any symptoms nor did he have a history of syncope. We propose that CPVT should be included in the differential diagnosis in children with recurrent episodes of syncope.     

Constitutive deficiency in DNA mismatch repair: is it time for Lynch III?

Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome types I and II, and the related subtypes Turcot and Muir-Torre syndrome, have all been associated with inheritance of germ line mutations in the DNA mismatch repair (MMR) genes. Fifty individuals have recently been identified with an early onset of a different spectrum of cancers associated with inheritance of two MMR mutations--resulting either in a constitutive loss of MMR function, or greatly impaired MMR function. In contrast to Lynch I and II individuals, individuals with inheritance of homozygous or compound heterozygous mutations in the MMR genes that result in a complete lack of protein, present with hematological and brain malignancies in the first decade of life. Biallelic mutations with compromised but residual protein function present with a broader spectrum of cancers (brain, hematological or gastrointestinal) in the second to fourth decades of life. We propose that inheritance of two MMR mutations in an individual and the unique tumor spectrum that occurs with an early onset should be defined separately from Lynch syndrome I and II, or the subtypes Turcot and Muir-Torre. We suggest Lynch III as an appropriate name for identifying individuals with constitutively compromised MMR associated with biallelic mutations.     

常染色体隐性遗传性皮肤松弛症的相关基因研究进展

常染色体隐性遗传性皮肤松弛症是遗传性皮肤松弛症的常见类型,其发病机制尚未完全明确,但其可能的致病基因功能及其下游信号通路逐渐成为当前的研究热点。对与皮肤松弛症相关的基因及相应的信号通路的深入研究不仅为明确其发病机制奠基了良好的基础,同时,也为指导优生优育咨询指明了方向。本文主要综述近年来与常染色体隐性遗传性皮肤松弛症发病相关的基因及其信号通路的最新研究进展。     

基于数据挖掘技术探讨郭勇教授治疗肝癌的用药规律

[目的] 探讨郭勇教授治疗肝癌的处方用药规律,传承名中医治疗肝癌的指导思想并推广应用。[方法] 收集郭师治疗肝癌的处方,基于信息管理系统软件建立数据库,统计药物使用频次,并对药物的药性、药味、归经等进行描述性分析。[结果] 药性频率最高的是寒(34.46%),其次是温(29.94%)、平(27.12%),累计频率达91.52%;药味频率最高的是甘(37.09%),其次是苦(23.64%)、辛(17.45%),累计频率达78.18%;药物归经频率最高的是肝(19.61%)、其次是脾(15.50%)、肺(15.25%)、胃(14.29%),累计频率达64.65%。采用关联法则、复杂网络分析、聚类分析等数据挖掘方法,确定处方中各种药物的使用频次和药物之间的关联规则,前6位中药依次为:白芍、郁金、预知子、猫爪草、猫人参、太子参。从核心处方总结出,郭师治疗肝癌多用猫人参、猫爪草、郁金、预知子、白芍等药物。[结论] 郭师治疗肝癌,重视辨病与辨证相结合,应用灵活,配伍严谨。数据挖掘应用对于挖掘名老中医临床经验具有重要的价值。