Investigation of the CACNA1A gene as a candidate for typical migraine susceptibility

Typical migraine is a complex neurological disorder comprised of two main subtypes: migraine with (MA) and without aura (MO). The disease etiology is still unclear, but family studies provide strong evidence that defective genes play an important role. Familial hemiplegic migraine (FHM) is a very rare and severe subtype of MA. It has been proposed that FHM and MA may have a similar genetic etiology. Therefore, genetic studies on FHM provide a useful model for investigating the more prevalent types of typical migraine. FHM in some families has been shown to be caused by mutations in a brain‐specific P/Q‐type calcium channel α1 subunit gene (CACNA1A) on chromosome 19p13. There has also been a report of a CACNA1A mutation being associated with MA in a patient from a family with predominant FHM. We have previously demonstrated suggestive linkage of typical migraine in a large Australian family to the FHM region on chromosome 19p13. These findings suggest that CACNA1A may also be implicated in the etiology of typical migraine in this pedigree. To investigate this possibility, we sequenced two patients carrying the critical susceptibility haplotype surrounding CACNA1A. No disease‐causing mutations or polymorphisms were revealed in any of the 47 exons screened. To determine whether the CACNA1A gene was implicated in typical migraine susceptibility in the general Caucasian population, we also analyzed 82 independent pedigrees and a large case control group. We did not detect any linkage or association in these groups and conclude that if CACNA1A plays a role in typical migraine, it does not confer a major effect on the disease. © 2001 Wiley‐Liss, Inc.     

Pre- and post-treatment FDG PET-CT as a predictor of patient outcomes in anal squamous cell carcinoma: A systematic review and meta-analysis

Anal squamous cell carcinoma (ASCC) has a generally acceptable outlook in terms of survival. 18-fluorodeoxyglucose-positron emission tomography/computer tomography (FDG PET-CT) is not recommended for routine monitoring post-ASCC treatment. We examine herein if FDG PET-CT has a use in the prognostic evaluation of patients with ASCC, what FDG PET-CT metrics are of value and if a pre- or post-chemo/radiotherapy scan is more prognostic of outcomes. PubMed, EMBASE and Cochrane Central Registry of Controlled Trials were comprehensively searched until 3 May, 2023. A modified Newcastle Ottawa scale was used to assess for study bias. We present our systematic review alongside pooled hazard ratios (HR) for maximum standardised uptake values (SUV) as a predictor of overall survival (OS) and progression-free survival (PFS). Seven studies including 523 patients were included in our systematic review. Current evidence suggests that SUV maximum and median, metabolic tumour volume, total lesion glycolysis and complete and partial metabolic response may be prognostic when considering overall or progression-free survival (OS)/(PFS) along with local recurrence (LR). Pooled HR from two included studies indicate SUV max is prognostic of OS, HR 1.179, CI (1.039–1.338), P = 0.011 and PFS 1.176, CI (1.076–1.285), P < 0.01. FDG PET-CT may have a role to play in the prognostic evaluation of ASCC patients. Current evidence suggests post-treatment scanning may hold superior prognostic value at this time.     

Investigation of the CACNA1A gene as a candidate for typical migraine susceptibility.

Typical migraine is a complex neurological disorder comprised of two main subtypes: migraine with (MA) and without aura (MO). The disease etiology is still unclear, but family studies provide strong evidence that defective genes play an important role. Familial hemiplegic migraine (FHM) is a very rare and severe subtype of MA. It has been proposed that FHM and MA may have a similar genetic etiology. Therefore, genetic studies on FHM provide a useful model for investigating the more prevalent types of typical migraine. FHM in some families has been shown to be caused by mutations in a brain-specific P/Q-type calcium channel alpha1 subunit gene (CACNA1A) on chromosome 19p13. There has also been a report of a CACNA1A mutation being associated with MA in a patient from a family with predominant FHM. We have previously demonstrated suggestive linkage of typical migraine in a large Australian family to the FHM region on chromosome 19p13. These findings suggest that CACNA1A may also be implicated in the etiology of typical migraine in this pedigree. To investigate this possibility, we sequenced two patients carrying the critical susceptibility haplotype surrounding CACNA1A. No disease-causing mutations or polymorphisms were revealed in any of the 47 exons screened. To determine whether the CACNA1A gene was implicated in typical migraine susceptibility in the general Caucasian population, we also analyzed 82 independent pedigrees and a large case control group. We did not detect any linkage or association in these groups and conclude that if CACNA1A plays a role in typical migraine, it does not confer a major effect on the disease.     

VARIATION IN THE VITAMIN D RECEPTOR GENE IS ASSOCIATED WITH MULTIPLE SCLEROSIS IN AN AUSTRALIAN POPULATION

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) resulting in accumulating neurological disability. The disorder is more prevalent at higher latitudes. To investigate VDR gene variation using three intragenic restriction fragment length polymorphisms (Apa I, Taq I and Fok I) in an Australian MS case-control population. One hundred and four Australian MS patients were studied with patients classified clinically as Relapsing Remitting MS (RR-MS), Secondary Progressive MS (SP-MS) or Primary Progressive MS (PP-MS). Also, 104 age-, sex-, and ethnicity-matched controls were investigated as a comparative group. Our results show a significant difference of genotype distribution frequency between the case and control groups for the functional exon 9 VDR marker Taq I (p_Gen = 0.016) and interestingly, a stronger difference for the allelic frequency (p_All = 0.0072). The Apa I alleles were also found to be associated with MS (p_All = 0.04) but genotype frequencies were not significantly different from controls (p_Gen = 0.1). The Taq and Apa variants are in very strong and significant linkage disequilibrium (D′ = 0.96, P < 0.0001). The genotypic associations are strongest for the progressive forms of MS (SP–MS and PP–MS). Our results support a role for the VDR gene increasing the risk of developing multiple sclerosis, particularly the progressive clinical subtypes of MS.     

A new immunoglobulin sub-class in the sheep

A new immunoglobulin sub-class, IgG1_A, has been defined in the sheep with the aid of an antibody prepared by immunizing goats with sheep IgG. The sub-class antigen is located on the Fc fragment and is carried by approximately 20 per cent of the IgG1 molecules. IgG1_A is lacking in the serum of some sheep and this appears to be under X-linked genetic control. No marked breed distribution was found for IgG1_A negativity.