Entity

Time filter

Source Type

Auckland, New Zealand

Rodrigues M.,Auckland City Hospital | Kidd A.,Canterbury Health Laboratories | Love D.R.,Diagnostic Genetics | Roxburgh R.,Auckland City Hospital | Roxburgh R.,University of Auckland
Journal of Clinical Neuroscience | Year: 2015

The New Zealand Neuromuscular Disease Registry (NZ NMD Registry) is part of the TREAT NMD Alliance, an international network that provides infrastructure ensuring the most promising new therapies reach neuromuscular patients as quickly as possible. Its main aim is to ensure that the most promising new therapies reach patients as quickly as possible. From the perspective of researchers interested in trialling treatments it is useful to have data on the pool of potential research participants. From a patient's perspective it is important to know what trials they can take part in. Both of these require a confirmed molecular diagnosis in the patient. Some therapeutic strategies not only require knowledge of which gene is affected but are targeted at specific mutations within the gene. In reviewing data held in the NZ NMD Registry it was noted that, of those diagnosed with a genetic condition, only 51% have a confirmed molecular genetic diagnosis. This low rate of genetic diagnosis is a potential barrier to research participation but can be removed with improved genetic technology and with changes in knowledge about and attitudes towards genetic testing. © 2014 Elsevier Ltd. All rights reserved. Source


Marquis-Nicholson R.,Diagnostic Genetics
Genetics and molecular research : GMR | Year: 2010

We developed a mutation-screening protocol for the ASS1 gene in order to guide clinical management of neonates with elevated citrulline detected during routine newborn screening. An exon-based amplification and sequencing method was designed and successfully applied to patients to identify disease-associated mutations. The sequencing-based method was applied to three patients with mild or asymptomatic clinical courses. Identification of a homozygous mutation in these patients, c.787G>A (p.Val263Met), led to the development of a tetra-primer ARMS-PCR method that successfully detected the mutation in DNA extracted from blood or from Guthrie card spots. Source


Jain R.,Auckland University of Technology | Von Hurst P.R.,Massey University | Stonehouse W.,Massey University | Love D.R.,Diagnostic Genetics | And 2 more authors.
Metabolism: Clinical and Experimental | Year: 2012

The objectives of the study were to determine associations between single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) gene and insulin resistance and the effects of these SNPs on changes in insulin sensitivity in response to vitamin D supplementation. The research described here was an extension of the Surya study. Genotyping of the Cdx-2, FokI, BsmI, ApaI, and TaqI SNPs was carried out on 239 South Asian women in New Zealand using polymerase chain reaction-based techniques. Associations of these genotypes and 3′ end haplotypes with insulin resistance were determined using multiple regression analysis. Associations between SNP genotypes and responses in insulin sensitivity to vitamin D supplementation (4000 IU vitamin D 3 per day) were also determined for a subset (81) of these women. BsmI BB, ApaI AA, and TaqI tt genotypes were significantly associated with lower insulin resistance compared with BsmI bb, ApaI aa, and TaqI TT, respectively, in the cohort of 239 women. Furthermore, homozygosity of the haplotypes baT and BAt was associated with higher and lower insulin resistance, respectively, compared with no copies of their respective alleles. Of the 81 subjects who were supplemented with vitamin D, women with the FokI Ff genotype showed a significantly greater improvement in insulin sensitivity (increase of 29.4 [2.9, 38.1]) compared with women with the FokI FF genotype (increase of 2.3 [-11.5, 10.1]). This study has highlighted the association of vitamin D responsiveness and insulin resistance with VDR gene polymorphisms. This is the first study to determine associations between all three. Genotyping of the VDR gene may provide a predictive measure for insulin resistance in response to vitamin D intervention. © 2012 Elsevier Inc. All rights reserved. Source


George A.M.,Diagnostic Genetics
Genetics and molecular research : GMR | Year: 2012

Chromosome microarray analysis of patients with developmental delay has provided evidence of small deletions or duplications associated with this clinical phenotype. In this context, a 7.1- to 8.7-Mb interstitial deletion of chromosome 16 is well documented, but within this interval a rare 200-kb deletion has recently been defined that appears to be associated with obesity, or developmental delay together with overgrowth. We report a patient carrying this rare deletion, who falls into the latter clinical category, but who also carries a second very rare deletion in 13q31.3. It remains unclear if this maternally inherited deletion acts as a second copy number variation leading to pathogenic variation, or is non-causal and the true modifiers are yet to be determined. Source


Earle N.,University of Auckland | Yeo Han D.,University of Auckland | Pilbrow A.,University of Otago | Crawford J.,Greenlane Paediatric and Congenital Cardiac Services | And 5 more authors.
Heart Rhythm | Year: 2014

Background Disease-modifying single nucleotide polymorphisms (SNPs) can help explain incomplete penetrance and variable expressivity in congenital long QT syndrome (LQTS) by altering susceptibility to arrhythmias. Objective The purpose of this study was to assess multiple arrhythmia SNPs (in 16 genes) in a distinct cohort of LQTS patients to identify modifier SNPs influencing the risk of sudden death. Methods This study included 273 patients with LQTS from the New Zealand Cardiac Inherited Disease Registry (154 long QT type 1, 96 long QT type 2, and 23 long QT type 3), including 31 patients who had experienced death or resuscitated sudden cardiac death (RSCD). Patients were genotyped for 29 SNPs and tested for associations with clinical events and QTc length. Caucasian (n = 220) and Pacific Islander/New Zealand Maori (n = 53) ethnic groups were analyzed separately. This subgroup of Polynesian ancestry has not been previously studied for LQTS in either presentation or outcome. Results In Caucasians, four SNPs at two risk loci (NOS1AP: rs12143842 and rs16847548; and KCNQ1: rs10798 and rs8234) were significantly associated with clinical events after correction for multiple testing. Patients homozygous for the risk allele of rs12143842 had an increased risk of death/RSCD [hazard ratio 10.15, 95% confidence interval (2.38, 43.34), q = 0.045). Several other SNPs showed trends toward association with QTc length and clinical events. Conclusion This study demonstrates that SNPs in NOS1AP and KCNQ1 are associated with an increased risk of cardiac events in LQTS patients, with the hazard ratio suggesting they have significant potential in clinical risk stratification. © 2014 Heart Rhythm Society. All rights reserved. Source

Discover hidden collaborations