Abnormalities of chromosome 1p in human neuroblastoma tumors and cell lines

Specific constitutional chromosome rearrangements have been described in a small number of individuals with two solid childhood tumors, retinoblastoma and Wilms' tumor. On the basis of these observation, a causal relationship between these chromosome abnormalities and tumorigenesis has been postulated.Though a specific constitutional chromosome abnormality has yet to be reported in association with neuroblastoma, another childhood tumor, we now confirm the involvement of a particular chromosome segment in structural abnormalities in cells from this tumor. Deletions or rearrangements of chromosome 1p were found in preparations from four of six neuroblastomas from individuals with normal constitutional karyotypes and in three of four permanent neuroblastoma cell lines. Structural abnormalities resulting in the loss or rearrangements of material from 1p (with the most frequent break point being 1p32 and with all rearrangements involving the apparent loss or rearrangement of material distal to 1p31, always including 1p34 to 1pter), represent the single most common class of chromosome aberrations in neuroblastoma. This suggests that the distal portion of 1p contains at least one gene involved in the development of neuroblastoma.     

Homozygous Mutation on the β-Globin Polyadenylation Signal in a Tunisian Patient with β-Thalassemia Intermedia and Coinheritance of Gilbert’s Syndrome

We report here the clinical, hematological and molecular data in a 50-year-old patient with β-thalassemia intermedia (β-TI) caused by a homozygous β⁺ mutation on the β-globin gene polyadenylation (polyA) signal (AATAAA>AAAAAA). β Haplotype analysis was accomplished by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Haplotype and framework analysis showed that this mutation is associated with the [????????+?+?+] β haplotype and framework 1 (CCGCT) (FW1). This mutation was previously reported in the heterozygous state in association with the codon 9 (+TA) mutation in a β-TI patient originating from Tunisia. To the best of our knowledge, this is the first report describing this mutation in the homozygous state. The case reported here, coinherited Gilbert’s syndrome, which is characterized by hyperbilirubinemia. This conclusion was reached by the investigation of the promoter region [A(TA)_nTAA] motif of the UGT1A1 gene, showing the (TA)₆/(TA)₇ genotype.     

Gilbert综合征16例临床分析

目的探讨Gilbert综合征临床、肝组织病理特点。方法对本院收治的16例Gilbert综合征患者的临床及病理资料进行分析。结果患者以男性为多,临床症状轻微,以黄疸、疲乏为多,可出现肝脾肿大;均有总胆红素及间接胆红素上升,总胆红素大多在35.2～65.5mol/L,间接胆红素23.7～50.3μmol/L。肝组织病理变化轻,5例有小叶肝细胞疏松变性,3例有肝板细胞排列拥挤,汇管区扩大2例,有少量中性粒细胞和/或淋巴细胞浸润。饥饿试验后间接胆红素升高1倍以上,苯巴比妥治疗后胆红素下降。结论Gil-bert综合征临床症状轻微,以血清间接胆红素反复升高为主要表现,肝组织病理变化轻,饥饿试验和苯巴比妥治疗试验有助于诊断,基因检测尿苷二磷酸葡萄糖醛酸转移酶同工酶UGT1A1基因启动子区突变则可确诊。预后好,可不治疗。     

Results of an orthopaedic survey in young patients with severe haemophilia in Spain

Summary.  This paper outlines the results obtained in a cross-sectional study of a group of young patients with severe haemophilia A and B. The primary aim of the study was to ascertain the level of orthopaedic complications in the group, the effects that these complications have on quality of life, and the medical resources used on these patients. The secondary aim was to relate their current orthopaedic state to the type of treatment received before the study. The study was carried out in 11 hospitals in Spain, where 70 severe haemophilia patients (factor VIII [FVIII] < 2%), with an average age of 21.6 and a median age of 22, and no inhibitors, were monitored. The percentage of patients suffering from articular complaints was 84.3% and 85.7% according to the Gilbert and Petterson scales, respectively. Furthermore, pain was reported in 16.1% of joints, most frequently in ankles. Using the SF-36 Health Survey, patients were observed to have a poorer quality of life relative to healthy controls. Despite high levels of both the coagulant factor given to patients and the financial resources dedicated to their treatment, the type of treatment (on demand and/or as secondary prophylaxis) provided to the young adults was found to be incapable of preventing haemophilic arthropathy and subsequent negative quality of life consequences.     

GILBERT SYNDROME ASSOCIATED WITH β-THALASSEMIA

The authors investigated whether the considerable variability in serum bilirubin levels (STB) found in transfusion-dependent &#103 -thalassemia, &#103 -thal intermedia, and heterozygous &#103 -thalassemia individuals could be related to the coexistence of Gilbert syndrome (GS). The promoter region [A(TA) n TAA] of the bilirubin UDP-glucuronosyltransferase gene (UGT1A1) was analyzed in a total of 128 &#103 -thalassemia individuals (108 transfusion-dependent &#103 -thal patients, 20 very mild &#103 -thal intermedia) and in 33 &#103 -thal heterozygotes. The control group consisted of 70 healthy children with no history of anemia. The frequency of GS genotype (TA) 7 /(TA) 7 did not differ significantly between the groups studied. A significant difference was observed between serum bilirubin levels (STB) and GS genotypes (TA) 7 /(TA) 7 and (TA) 6 /(TA) 7 and also between (TA) 7 /(TA) 7 and (TA) 6 /(TA) 6 for all groups examined. These results confirm that the (TA) 7 /(TA) 7 GS genotype is one of the factors accounting for the hyperbilirubinemia observed in &#103 -thalassemia major, intermedia, and heterozygous individuals.     

一个中国Gilbert综合征家系的临床和遗传学特征分析

目的 通过对1个中国Gilbert综合征家系成员临床特征分析,结合致病基因尿苷二磷酸葡萄糖醛酸转移酶1A1(UGT1A1)基因已知突变位点鉴定,了解该病临床发病特点和分子遗传学基础.方法 在长期追踪先证者基础上,抽取先证者及其家系成员外周血,进行肝脏生化学、病原学和UGT1A1基因突变位点检测,排除相关疾病,PCR扩增启动子和外显子常见突变位点,产物直接测序鉴定基因型.结果 在该家系中,检测到3个突变位点:c.-3279T＞G、TA插入和Gly71Arg,并且C.-3279T＞G和TA插入存在连锁不平衡,其中4例患者中3例为杂合突变,1例为纯合突变,胆红素水平与UGT1A1基因型和表型相关.结论 c.-3279T＞G、TA插入和Gly71Arg突变可能与中国人群Gilbert综合征发生相关,该家系基本符合常染色体隐性遗传方式.