A Case of Partial Trisomy of Chromosome 8p Associated with Autism

We report on a case of a 6-year-old female with partial trisomy 8p(21–23) associated with autism, mild dysmorphic features, and moderate learning disability. Although mental retardation is a common finding in patients with mosaic trisomy 8 or partial trisomy of various regions of chromosome 8, only two cases associated with autism have been reported so far. Also, in our case clinical manifestations were mild compared to other patients with duplication of the same region of chromosome 8. Although there has been no strong evidence for linkage on chromosome 8 in any of the genome-wide linkage studies so far, the possibility that this segment includes genes involved in the etiology of autism should be further explored.     

Late-onset hereditary sensory neuropathy type I due to SPTLC1 mutation: autopsy findings

There is little published information on the autopsy findings in hereditary sensory neuropathy type I (HSN I), and none in genetically confirmed cases. We report the neuropathological findings in a 93-year-old woman with a disease of unusually late onset, who was part of a large HSN I kindred and in whom genetic analysis confirmed an SPTLC1 T399G mutation.     

Prediction of treatment response by HPA-axis and glucocorticoid receptor polymorphisms in major depression

OBJECTIVE: We investigated whether treatment response is predicted by hypothalamus-pituitary-adrenal (HPA) axis parameters, or by genetic polymorphisms in the glucocorticoid receptor (GR), that regulates its feedback. METHODS: Ninety-eight outpatients completed 8 weeks of paroxetine treatment. Treatment response was defined as a 50% decrease in Hamilton Rating Scale for depression (HRSD) ratings. At baseline, 24h urinary cortisol excretion, and cortisol and ACTH concentrations in a DEX/CRH test were measured. The presence of polymorphisms in the GR DNA sequence (BclI, ER22/23EK, N363S) was determined. Prediction of treatment response was analysed by calculating response rates per tertile of an HPA-axis parameter and per GR genotype. RESULTS: The response rate in the high ACTH tertile was significantly lower as compared to the intermediate tertile, but not compared to the low tertile (response rates from high to low tertile: 33%, 67% and 42%). Carriers of the BclI polymorphism had higher ACTH values than non-carriers (baseline ACTH: 3 versus 5ng/l, p=0.02) and showed a trend towards lower decrease of HRSD rates than non-carriers (HRSD decrease: 8 versus 11, respectively, p=0.07). In a subgroup of BclI carriers, patients in the high ACTH tertile had a lower decrease in HRSD and lower response rates than patients in the low ACTH tertiles (HRSD decrease from high to low tertile: 5, 9 and 11, p<0.01). CONCLUSION: The results suggest that hyperactivity of the HPA-axis predict worse treatment outcome. The BclI polymorphism explains, in part, DEX/CRH test results and tends to be associated with worse treatment outcome.     

Association between plasma activities of semicarbazide-sensitive amine oxidase and angiotensin-converting enzyme in patients with type 1 diabetes mellitus

Aims/hypothesis Plasma semicarbazide-sensitive amine oxidase (SSAO) is elevated in patients with type 1 and type 2 diabetes and has been implicated in the pathophysiology of diabetic late complications. The regulation of SSAO production remains unknown. We studied correlations between plasma SSAO activity and parameters associated with diabetic late complications.Methods Plasma SSAO was measured in a well-characterised group of 287 patients with type 1 diabetes. Standard statistical methods were used to investigate correlations with clinical parameters and components of the renin–angiotensin system.Results Overall, plasma SSAO was elevated, at 693±196 mU/l (mean±SD; normal controls 352±102 mU/l). Plasma SSAO was higher in the group with late complications or hypertension, and in patients treated with ACE-inhibitors. In univariate analysis a significant positive correlation (p<0.001, r=0.27) was found between plasma SSAO and serum ACE activity in patients untreated with ACE inhibitors or angiotensin II receptor antagonists (n=221), but plasma SSAO did not differ by ACE I/D genotype. Plasma SSAO correlated positively with duration of diabetes, HbA₁c and plasma renin, and negatively with plasma angiotensinogen and body mass index. A multiple regression analysis including these variables resulted in serum ACE activity (p<0.001), ACE genotype (negatively, p<0.001) and HbA₁c (p=0.023) as explaining variables.Conclusions/interpretation Results suggest that a common factor is involved in the regulation of both plasma SSAO and serum ACE, which is different from the genetic determination of ACE activity.     

The association between acute fatty liver of pregnancy and fatty acid oxidation disorders

Acute fatty liver of pregnancy is a relatively rare but potentially fatal liver disorder of late pregnancy. Recent advances in molecular diagnostic procedures provide evidence of a genetic basis for this condition and a link to offspring disorders in fatty acid oxidation. This relationship implies the need for genetic testing and follow-up of at-risk women and their neonates.     

Leukotriene-related gene polymorphisms in patients with aspirin-intolerant urticaria and aspirin-intolerant asthma: differing contributions of ALOX5 polymorphism in Korean population

The pathogenesis of aspirin (acetylsalicylic acid, ASA)-intolerant urticaria (AIU) is still poorly understood but it has recently been suggested that it is associated with the overproduction of leukotriene (LT). This is supported by evidence that cyclooxygenase 2 inhibitor is given safely to patients with AIU. The present study was designed to investigate the role of genetic polymorphism of LT related genes in the pathogenesis of AIU via a case-control study. We screened single nucleotide polymorphisms (SNPs) in genes encoding enzymes involved in leukotriene synthesis in the Korean population with AIU (n = 101), ASA-intolerant asthma (AIA, n = 95) and normal healthy controls (n = 123). Genotype was determined by primer extension reactions using the SNapShot ddNTP primer extension kit. Among 8 SNPs of four LT related genes, the polymorphism of ALOX5 at positions of -1708 G > A showed significant difference in genotype frequency between AIU and AIA (p = 0.01). Furthermore, there were significant differences observed in the frequencies of two ALOX5 haplotypes between the AIU group and AIA group (p < 0.05). However, there were no differences in allele, genotype, or haplotype frequencies of ALOX5 between the AIU group and the normal control group. These results suggested that ALOX5 has a differing contribution in two major clinical pathogenesis related to ASA-sensitivity.     

Craniofacial syndromes

The neonate with cranio-facial dysmorphism presents a difficult diagnostic problem as only a limited number of cranio-facial syndromes can be diagnosed with confidence in the neonatal period. This review outlines a systematic approach to this problem and discusses the genetic aspects and clinical features of the common cranio-facial syndromes that can be diagnosed in the neonatal period.     

Thymoma and Thymic Carcinoma: An Update of the WHO Classification 2004

When dealing with tumors of the thymus and mediastinum, both the surgeon and the pathologist are confronted with a vast variety of different pathohistologic entities, among which epithelial tumors, namely thymomas and thymic carcinomas, are the most frequent. Intimate knowledge of the different entities and their anticipated clinical outcome is required to meet diagnostic and therapeutic challenges. We herein briefly update the reader with the most important new changes in the 2004 WHO classification of tumors of the thymus and to important new trends in the treatment of some of these tumors.     

Congenital heart defects: 15 years of experience of the Emilia-Romagna Registry (Italy)

Objectives: Collection and assessment of data from the Emilia-Romagna Region on the occurrence of congenital heart defects in order to identify an homogeneous group of patients for further aetiologic and genetic studies. Materials and methods: The present study is based on 1549 stillborn and live born babies affected by congenital heart defect out of 330,017 consecutive births (4.7 per 1000). Results: The frequency and type of congenital heart defects have been identified together with the sex ratio, associated extracardiac anomalies, chromosomal anomalies and the risk of precurrence in relatives. The impact of prenatal diagnosis on prevalence was low during the study period. Conclusions: The study has provided epidemiological data for public health surveillance of congenital heart defects in the Emilia-Romagna region. The creation of a system for the nationwide recording of congenital heart defects designed with regard to the sources of ascertainment, the diagnostic criteria, and the system of classification is emphasised.