-
[show abstract]
[hide abstract]
ABSTRACT: The Genetic Resource Centre is a centralized process for requesting genetic testing that is not available within the province (Alberta, Canada). In order to assess potential cost savings associated with this process, all applications received by the Genetic Resource Centre in 2010 were reviewed, and cost savings were recorded for statistical analysis. Seven areas of cost savings were identified:Negotiated pricing;Laboratory selection;Testing set up in province;Duplicate testing;Inappropriate testing;Sequential testing and;Testing offered within the province. The total test cost of the 615 applications submitted in 2010 without the GRC process would have been $766 783 (Canadian dollars). A total cost savings of $112 201 was achieved through the GRC, which represents 15% of the total cost of requested testing ($112 201/$766 783). This is the first study to examine areas of cost savings for genetic testing sent out -of-province. The greatest cost savings resulted from the areas of laboratory selection and negotiated pricing. A centralized process to manage out-of-province genetic test requests results in consistency in testing and significant cost savings.
Clinical Genetics 12/2012; · 3.13 Impact Factor
-
Patrick Scott,
Lynn Podemski,
Kelly Baptista Wyatt,
Christine Walker,
Shelagh M Haase,
Basil G Elyas,
Kathleen A Sprysak, Margaret Lilley,
Susan Christian,
Mark Hicks,
Martin J Somerville,
Stacey L Hume
[show abstract]
[hide abstract]
ABSTRACT: To evaluate and compare the performance of the recently released Aneufast™ v2 (MolgentixSL) and QST*RplusV2 commercial assays (Gen-Probe), both designed for the quantitative fluorescent-polymerase chain reaction (PCR) detection of the common aneuploidies during pregnancy.
A series of 160 consecutive fetal samples referred for rapid aneuploidy detection testing and an additional 25 samples enriched for the presence of an abnormality were selected for comparison.
To confidently rule out a chromosome abnormality, a second round of short tandem repeat typing was required for 14.1% (26) and 9.7% (18) of the specimens analyzed with Aneufast v2 and QST*RplusV2, respectively. Reflex testing was required for 7.6% (14) and 5.9% (11) of the specimens analyzed with respective assays to confidently rule out an autosomal trisomy. For the sex chromosomes, the difference in the amount of follow-up testing is greater between the assays, as a result of the inclusion in the initial PCR of the TAF9L paralogous marker in the QST*RplusV2 assay.
Overall, both assays performed similarly in the detection of aneuploidies. In this sample set, the QST*RplusV2 kit required less frequent reflex testing, which translates into shorter turnaround time and cost savings. The incorporation of the TAF9L paralogous sequence in the initial PCR is advantageous for diagnostic use.
Genetic Testing and Molecular Biomarkers 06/2012; 16(8):943-7. · 1.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: An increasing number of genetic counselors are moving into non-clinical roles, where their primary duties do not involve direct patient contact. According to the National Society of Genetic Counselors Professional Status Survey in 2010, 23% of counselors working in non-clinical roles identified laboratory or genetic testing as their primary area of work. Using a survey, we identified 43 genetic counselors who work predominately in laboratory settings. The two primary tasks performed by participants, include acting as a customer liaison (95%) and calling out test results (88%). Nineteen participants (44.2%) also reported spending a considerable amount of time signing reports. The most prevalent areas of job satisfaction were support from laboratory directors (76.8%), autonomy (76.7%), interactions with clinicians (69.7%) and interaction with other genetics counselors (67.5%). This is the first study specifically looking at the roles of laboratory genetic counselors, which is an expanding area of genetic counseling.
Journal of Genetic Counseling 11/2011; 21(4):605-11. · 1.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: On April 1, 2007, Alberta became the first province in Canada to introduce cystic fibrosis (CF) to its newborn screening program. The Alberta protocol involves a two-tier algorithm involving an immunoreactive trypsinogen measurement followed by molecular analysis using a CF panel for 39 mutations. Positive screens are followed up with sweat chloride testing and an assessment by a CF specialist. Of the 99,408 newborns screened in Alberta during the first two years of the program, 221 had a positive CF newborn screen. The program subsequently identified and initiated treatment in 31 newborns with CF. A relatively high frequency of the R117H mutation and the M1101K mutation was noted. The M1101K mutation is common in the Hutterite population. The presence of the R117H mutation has created both counselling and management dilemmas. The ability to offer CF transmembrane regulator full sequencing may help resolve diagnostic dilemmas. Counselling and management challenges are created when mutations are mild or of unknown clinical significance.
Paediatrics & child health 11/2010; 15(9):590-4. · 0.78 Impact Factor
-
Girish V Putcha,
Bassem A Bejjani,
Stacey Bleoo,
Jessica K Booker,
John C Carey,
Nancy Carson,
Soma Das,
Melissa A Dempsey,
Julie M Gastier-Foster,
John H Greinwald, [......],
Fred Schaefer,
William K Seltzer,
Elaine B Spector,
Michelle A Springer,
Karen E Weck,
Richard J Wenstrup,
Stacey Withrow,
Bai-Lin Wu,
Maimoona A Zariwala,
Iris Schrijver
[show abstract]
[hide abstract]
ABSTRACT: The aim of the study was to determine the actual GJB2 and GJB6 mutation frequencies in North America after several years of generalized testing for autosomal recessive nonsyndromic sensorineural hearing loss to help guide diagnostic testing algorithms, especially in light of molecular diagnostic follow-up to universal newborn hearing screening.
Mutation types, frequencies, ethnic distributions, and genotype-phenotype correlations for GJB2 and GJB6 were assessed in a very large North American cohort.
GJB2 variants were identified in 1796 (24.3%) of the 7401 individuals examined, with 399 (5.4%) homozygous and 429 (5.8%) compound heterozygous. GJB6 deletion testing was performed in 12.0% (888/7401) of all cases. The >300-kb deletion was identified in only nine individuals (1.0%), all of whom were compound heterozygous for mutations in GJB2 and GJB6. Among a total of 139 GJB2 variants identified, 53 (38.1%) were previously unreported, presumably representing novel pathogenic or benign variants.
The frequency and distribution of sequence changes in GJB2 and GJB6 in North America differ from those previously reported, suggesting a considerable role for loci other than GJB2 and GJB6 in the etiology of autosomal recessive nonsyndromic sensorineural hearing loss, with minimal prevalence of the GJB6 deletion.
Genetics in Medicine 07/2007; 9(7):413-26. · 4.76 Impact Factor
-
Martin J Somerville,
Carolyn B Mervis,
Edwin J Young,
Eul-Ju Seo,
Miguel del Campo,
Stephen Bamforth,
Ella Peregrine,
Wayne Loo, Margaret Lilley,
Luis A Pérez-Jurado,
Colleen A Morris,
Stephen W Scherer,
Lucy R Osborne
[show abstract]
[hide abstract]
ABSTRACT: The Williams-Beuren syndrome (WBS) locus, at 7q11.23, is prone to recurrent chromosomal rearrangements, including the microdeletion that causes WBS, a multisystem condition with characteristic cardiovascular, cognitive, and behavioral features. It is hypothesized that reciprocal duplications of the WBS interval should also occur, and here we present such a case description. The most striking phenotype was a severe delay in expressive speech, in contrast to the normal articulation and fluent expressive language observed in persons with WBS. Our results suggest that specific genes at 7q11.23 are exquisitely sensitive to dosage alterations that can influence human language and visuospatial capabilities.
New England Journal of Medicine 11/2005; 353(16):1694-701. · 53.30 Impact Factor
-
Twila M Yobb,
Martin J Somerville,
Lionel Willatt,
Helen V Firth,
Karen Harrison,
Jennifer MacKenzie,
Natasha Gallo,
Bernice E Morrow,
Lisa G Shaffer,
Melanie Babcock,
Judy Chernos,
Francois Bernier,
Kathy Sprysak,
Jesse Christiansen,
Shelagh Haase,
Basil Elyas, Margaret Lilley,
Steven Bamforth,
Heather E McDermid
[show abstract]
[hide abstract]
ABSTRACT: 22q11.2 microduplications of a 3-Mb region surrounded by low-copy repeats should be, theoretically, as frequent as the deletions of this region; however, few microduplications have been reported. We show that the phenotype of these patients with microduplications is extremely diverse, ranging from normal to behavioral abnormalities to multiple defects, only some of which are reminiscent of the 22q11.2 deletion syndrome. This diversity will make ascertainment difficult and will necessitate a rapid-screening method. We demonstrate the utility of four different screening methods. Although all the screening techniques give unique information, the efficiency of real-time polymerase chain reaction allowed the discovery of two 22q11.2 microduplications in a series of 275 females who tested negative for fragile X syndrome, thus widening the phenotypic diversity. Ascertainment of the fragile X-negative cohort was twice that of the cohort screened for the 22q11.2 deletion. We also report the first patient with a 22q11.2 triplication and show that this patient's mother carries a 22q11.2 microduplication. We strongly recommend that other family members of patients with 22q11.2 microduplications also be tested, since we found several phenotypically normal parents who were carriers of the chromosomal abnormality.
The American Journal of Human Genetics 06/2005; 76(5):865-76. · 10.60 Impact Factor
-
Jesse Christiansen,
John D Dyck,
Basil G Elyas, Margaret Lilley,
J Stephen Bamforth,
Mark Hicks,
Kathleen A Sprysak,
Robert Tomaszewski,
Shelagh M Haase,
Leanne M Vicen-Wyhony,
Martin J Somerville
[show abstract]
[hide abstract]
ABSTRACT: Congenital heart disease (CHD), comprising structural or functional abnormalities present at birth, is the most common birth defect in humans. Reduced expression of connexin40 (Cx40) has been found in association with atrial fibrillation, and deletion of Cx40 in a mouse model causes various structural heart abnormalities in 18% of heterozygotes. We screened 505 unrelated CHD cases for deletions or duplications of the Cx40 gene (GJA5) by real-time quantitative PCR, in order to determine whether altered copy number of this gene may be associated with a cardiac phenotype in humans. Dosage of Cx40 flanking genes (ACPL1 and Cx50 gene, GJA8) was determined by real-time PCR for all apparent positive cases. In total, 3 cases were found to carry deletions on chromosome 1q21.1 spanning ACPL1, Cx40, and Cx50 genes. Absence of heterozygosity was observed in all 3 index cases over a 1.5- to 3-Mb region. Samples from the parents of two cases were obtained, and microsatellites across 1q21.1 were genotyped. One of the apparently unaffected parents was found to carry this deletion. All 3 index cases presented with obstruction of the aortic arch as the common structural cardiac malformation, and had no consistent dysmorphic features. Genotyping of 520 unrelated normal controls for this deletion was negative. We hypothesize that this 1q21.1 multigene deletion is associated with a range of cardiac defects, with anomalies of the aortic arch being a particular feature.
Circulation Research 07/2004; 94(11):1429-35. · 9.49 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Pancreatic cancer is known to aggregate in some families and has been associated with a wide variety of cancer syndromes. The authors describe their experience with pancreatic cancer and the range of associated cancer syndromes.
The charts of all patients seen for concern of a hereditary cancer syndrome in the Cancer Genetics Clinic at the University of Alberta between 1995 and 2002 were reviewed.
Forty families reported a personal or family history of pancreatic cancer in the context of a possible hereditary cancer syndrome. Three additional families reported a history of pancreatitis. Twenty-four (56%) of those families were suspected of having a hereditary breast and ovarian cancer syndrome. A further seven (16%) were suspected of having hereditary nonpolyposis colon cancer. Only three (7%) were believed to be at risk for a site-specific pancreatic cancer syndrome. Another three (7%) were suspicious for hereditary pancreatitis. The remaining family histories were suggestive of Li-Fraumeni syndrome, von Hippel-Lindau syndrome or a nonspecific cancer predisposition.
With such a wide variety of hereditary cancer syndromes associated with pancreatic cancer, an accurate assessment of the family history is essential to determine the most appropriate cancer screening for at-risk family members and to guide any molecular testing that may be offered.
Canadian journal of gastroenterology = Journal canadien de gastroenterologie 02/2004; 18(1):17-21. · 1.21 Impact Factor
