An analysis of clinical characteristics in genetically linked migraine-affected pedigrees

Migraine is a common complex disorder characterized by severe recurrent headache and usually accompanied by nausea and vomiting. Previous studies in our laboratory have utilized three large multigenerational Australian pedigrees affected with migraine to indicate that the disease is genetically heterogeneous, with linkage results implicating genomic susceptibility regions on both chromosomes 19p and Xq. The present study explores the possibility of a correlation between genetic and clinical heterogeneity in these affected pedigrees. Specifically, the clinical characteristics of migraine including subtype, age of onset, frequency, duration, and disease symptoms were compared between the migraine pedigrees, and gender differences were also assessed. Our exploratory analyses revealed no significant differences in any of the clinical characteristics tested between the chromosome 19-linked family and the two X-linked families. Also, we did not detect any differences in male vs. female clinical features for these pedigrees. In conclusion, migraine is considered to be a clinically and genetically heterogeneous disorder; however, our study provided no conclusive evidence that variation in genomic susceptibility region is related to heterogeneity at the clinical level in these migraine-affected pedigrees.

Psychiatric genetics in Australia

Australian research in psychiatric genetics covers molecular genetic studies of depression, anxiety, alcohol dependence, Alzheimer's disease, bipolar disorder, schizophrenia, autism, and attention deficit hyperactivity disorder. For each disorder, a variety of clinical cohorts have been recruited including affected sib pair families, trios, case/controls, and twins from a large population-based twin registry. These studies are taking place both independently and in collaboration with international groups. Microarray studies now complement DNA investigations, while animal models are in development An Australian government genome facility provides a high throughput genotyping and mutation detection service to the Australian scientific community, enhancing the contribution of Australian psychiatric genetics groups to gene discovery. (C) 2003 Lippincott Williams Wilkins.

Survey of ferroxidase expression and siderophore production in clinical isolates of Pseudomonas aeruginosa

Ferroxidase (encoded by the mco gene), a component of a ferrous iron uptake pathway in Pseudomonas aeruginosa, was detected in all of the 35 respiratory clinical isolates surveyed; in contrast, considerable variation in siderophore expression was observed. The ubiquitous expression of this periplasmic ferroxidase suggests that it plays a key role in iron uptake in this opportunistic pathogen.

The molecular genetics of breast cancer: The contribution of comparative genomic hybridization

Comparative genomic hybridization (CGH) has been the technique of choice over the last 10 years for mapping DNA copy number changes in human tumors. Here we review the literature to demonstrate how CGH has contributed to the comprehension of molecular aspects of breast tumorigenesis. At least two distinct molecular pathways of breast cancer have been characterized that show a strong correlation with histological grade. It seems that grade I invasive ductal carcinomas (IDCs) arise from well-differentiated ductal carcinoma in situ (DCIS), whereas grade III IDCs come from poorly differentiated DCIS. In addition, dedifferentiation from a low- to a high-grade breast cancer has proven an unlikely phenomenon. CGH has been instrumental in dissecting distinct molecular pathways toward breast malignancy and in establishing a direct relationship between genotype and clinical pathological features. (C) 2005 Elsevier GrnbH. All rights reserved.

A report of a national mutation testing service for the MEN1 gene: clinical presentations and implications for mutation testing

Introduction: Mutation testing for the MEN1 gene is a useful method to diagnose and predict individuals who either have or will develop multiple endocrine neoplasia type 1 ( MEN 1). Clinical selection criteria to identify patients who should be tested are needed, as mutation analysis is costly and time consuming. This study is a report of an Australian national mutation testing service for the MEN1 gene from referred patients with classical MEN 1 and various MEN 1- like conditions. Results: All 55 MEN1 mutation positive patients had a family history of hyperparathyroidism, had hyperparathyroidism with one other MEN1 related tumour, or had hyperparathyroidism with multiglandular hyperplasia at a young age. We found 42 separate mutations and six recurring mutations from unrelated families, and evidence for a founder effect in five families with the same mutation. Discussion: Our results indicate that mutations in genes other than MEN1 may cause familial isolated hyperparathyroidism and familial isolated pituitary tumours. Conclusions: We therefore suggest that routine germline MEN1 mutation testing of all cases of classical'' MEN1, familial hyperparathyroidism, and sporadic hyperparathyroidism with one other MEN1 related condition is justified by national testing services. We do not recommend routine sequencing of the promoter region between nucleotides 1234 and 1758 ( Genbank accession no. U93237) as we could not detect any sequence variations within this region in any familial or sporadic cases of MEN1 related conditions lacking a MEN1 mutation. We also suggest that testing be considered for patients < 30 years old with sporadic hyperparathyroidism and multigland hyperplasia

Atypical prostatic glandular proliferations on needle biopsy - Diagnostic implications, use of immunohistochemistry, and clinical significance

In recent times, PSA screening and a substantial increase in prostate needle biopsies have not only resulted in detection of minute foci of cancer but have also very likely resulted in increased detection of atypical glandular proliferations. Not uncommonly, there are only a limited number of atypical glands in these biopsies, and these require careful evaluation to enable an accurate diagnosis. We describe diagnostic implications, use of immunohistochemistry, and clinical significance of these lesions. Foci of atypical glands, also labeled atypical small acinar proliferation of uncertain significance, have features suspicious for but not diagnostic of cancer. Atypical foci include a broad group of lesions of differing clinical significance. These include benign, small acinar proliferations mimicking prostate cancer and atypical glandular proliferations suspicious for carcinoma. Definite diagnosis requires accurate histopathologic assessment and judicious use of immunohistochemistry. Patients with atypical glands on prostate needle biopsy have a high risk for harboring cancer and therefore have an increased risk for having cancer detected in subsequent biopsies.

Non-major-histocompatibility-complex genetics of ankylosing spondylitis

There is strong evidence from twin and family studies indicating that a substantial proportion of the heritability of susceptibility to ankylosing spondylitis (AS) and its clinical manifestations is encoded by non-major-histocompatibility-complex genes. Efforts to identify these genes have included genomewide linkage studies and candidate gene association studies. One region, the interleukin (IL)-I gene complex on chromosome 2, has been repeatedly associated with AS in both Caucasians and Asians. It is likely that more than one gene in this complex is involved in AS, with the strongest evidence to date implicating IL-IA. Identifying the genes underlying other linkage regions has been difficult due to the lack of obvious candidates and the low power of most studies to date to identify genes of the small to moderate magnitude that are likely to be involved. The field is moving towards genomewide association analysis, involving much larger datasets of unrelated cases and controls. Early successes using this approach in other diseases indicates that it is likely to identify genes in common diseases like AS, but there remains the risk that the common-variant, common-disease hypothesis will not hold true in AS. Nonetheless, it is appropriate for the field to be cautiously optimistic that the next few years will bring great advances in our understanding of the genetics of this condition.