French-Canadian Population Research Articles

Development of a French-Canadian Version of the Oswestry Disability Index

Cross-cultural translation and psychometric testing. To translate, culturally adapt, and validate the Oswestry Disability Index (ODI) version 2.0 for the French-Canadian population. Many authors have recommended the administration of standardized instruments, rather than the creation of new scales, and advocate the adaptation of validated questionnaires in other languages. The application of these scales in different countries and by cultural groups necessitates cross-cultural adaptation. Many scales evaluate the functional incapacity resulting from low back pain. The ODI is among the most commonly used for this purpose. The French-Canadian ODI (ODI-FC) was developed by cross-cultural adaptation following internationally recommended methodology: forward translation, back translation, expert committee revision, and clinical evaluation of the prefinal version. Psychometric testing was performed on 72 patients with chronic low back pain. The subjects were recruited from a physiatry department in a university hospital and from a private practice physiatry clinic. They came from the Montreal area. The psychometric testing included internal consistency (Cronbach α), test-retest reliability (intraclass correlation coefficient) with a time interval set at 48 hours, and construct validity, comparing the ODI-FC with the Roland-Morris Disability Questionnaire and the Quebec Back Pain Disability Scale (Pearson correlation coefficient). In 44.4% of the subjects, the average duration of low-back pain varied between 1 and 5 years. Average score for the ODI-FC was 29.2. Good internal consistency was found (Cronbach α = 0.88). Reliability was excellent, with intraclass correlation coefficient = 0.92 (95% confidence interval, 0.87-0.95). Construct validity results revealed excellent correlations between the ODI and the Quebec Back Pain Disability Scale (r = 0.90) and between the ODI and the Roland-Morris Disability Questionnaire (r = 0.84). Cross-cultural translation and adaptation of the ODI-FC were successful. Psychometric testing determined that the instrument was homogeneous, reliable, and valid. It could be employed in future clinical trials in Canada and possibly in other French-speaking countries.

Screening of three Mediterranean phenylketonuria mutations in Tunisian families

Phenylketonuria (PKU; OMIM 261600) is an autosomal recessive disease caused by the liver phenylalanine hydroxylase (PAH) enzyme (EC1.14.16.1) deficiency. If untreated, causes mental retardation. The incidence in Caucasian population is approximately 1:10,000 (Scriver and Kaufman 2001). In Tunisia, it seems to be more frequent with a prevalence of 1 in 7631 (Khemir et al. 2011). To this date, more than 530 mutations in the PAH gene (12q22-q24) have been described (http://www. pahdb.mcgill.ca). The characterization of PKU mutations has been made in many countries, all over the world; nevertheless, to date few studies have been reported on the North African populations. In Mediterranean countries, several mutations have been reported. The most common: IVS10–11G>A seems to be widespread. The G352Vfs delG was reported in Algerian, Italian, French Canadian, Croatian and Lebanese populations (Lyonnet et al. 1989); in Morocco, it was described as the most frequent mutation (Dahri et al. 2010). The E280K mutation was also reported in Mediterranean populations (Guldberg et al. 1993). Since Tunisia is a Mediterranean country, patients with PKU are presumed to have these mutations. The aim of this study was to assess prevalence of the three above mutations among PKU patients collected from paediatric departments of hospitals in Tunis.

Mutations in C5ORF42 Cause Joubert Syndrome in the French Canadian Population

Joubert syndrome (JBTS) is an autosomal-recessive disorder characterized by a distinctive mid-hindbrain malformation, developmental delay with hypotonia, ocular-motor apraxia, and breathing abnormalities. Although JBTS was first described more than 40 years ago in French Canadian siblings, the causal mutations have not yet been identified in this family nor in most French Canadian individuals subsequently described. We ascertained a cluster of 16 JBTS-affected individuals from 11 families living in the Lower St. Lawrence region. SNP genotyping excluded the presence of a common homozygous mutation that would explain the clustering of these individuals. Exome sequencing performed on 15 subjects showed that nine affected individuals from seven families (including the original JBTS family) carried rare compound-heterozygous mutations in C5ORF42. Two missense variants (c.4006C>T [p.Arg1336Trp] and c.4690G>A [p.Ala1564Thr]) and a splicing mutation (c.7400+1G>A), which causes exon skipping, were found in multiple subjects that were not known to be related, whereas three other truncating mutations (c.6407del [p.Pro2136Hisfs*31], c.4804C>T [p.Arg1602*], and c.7477C>T [p.Arg2493*]) were identified in single individuals. None of the unaffected first-degree relatives were compound heterozygous for these mutations. Moreover, none of the six putative mutations were detected among 477 French Canadian controls. Our data suggest that mutations in C5ORF42 explain a large portion of French Canadian individuals with JBTS.

Identification and Characterization of BRCA1 and BRCA2 Founder Mutations

A large number of cancer predisposing BRCA1/BRCA2 mutations have been reported, with a wide variety among populations. In some restricted groups, specific germline mutations in these tumor suppressor genes have been found with high predominance, due to a founder effect. We focused our review on the Italian founder mutations. The first Italian BRCA1 founder mutation, 5083del19, was found in Calabria: the presence of common allele in all carriers of this mutation (also in families with Calabrian origin living in other parts of Italy) confirmed its founder effect. The same BRCA1 mutation was identified in the Sicilian population, but only the haplotype analysis can reveal the common ancestor of these groups. Another BRCA1 founder mutation, 4843delC, was found in Sicily. Four distinct BRCA1 mutations are attributable to families original from Tuscany: 3348delAG, 3285delA, 1499insA and 5183delTGT; the latter has been shown to be a founder mutation from North-Eastern Italy. The first BRCA2 mutation was identified in Sardinia, 8765delAG, a mutation already described as a founder mutation in Jewish-Yemenite families and also in French-Canadian population but with independent origins of carriers in these three populations. BRCA2 3951del3 and BRCA1 917delTT have been described as founder mutations in Middle Sardinia and in South and Middle Sardinia, respectively. Studies regarding prevalence and penetrance of founder mutations can allow to quantify the degree of homogeneity within a population and can surely help the geneticist and oncologist to simplify their choices in the genetic testing on high-risk families, on the basis of their ethnical origin. Keywords: BRCA1, BRCA2, founder mutation, Italian BRCA1, BRCA2 3951del3, BRCA1 917delTT, BRCA1 5083del19, BRCA1 3348delAG, BRCA2 8765delAG, BRCA1 Val1688del

Evidence for evolution in response to natural selection in a contemporary human population

It is often claimed that modern humans have stopped evolving because cultural and technological advancements have annihilated natural selection. In contrast, recent studies show that selection can be strong in contemporary populations. However, detecting a response to selection is particularly challenging; previous evidence from wild animals has been criticized for both applying anticonservative statistical tests and failing to consider random genetic drift. Here we study life-history variation in an insular preindustrial French-Canadian population and apply a recently proposed conservative approach to testing microevolutionary responses to selection. As reported for other such societies, natural selection favored an earlier age at first reproduction (AFR) among women. AFR was also highly heritable and genetically correlated to fitness, predicting a microevolutionary change toward earlier reproduction. In agreement with this prediction, AFR declined from about 26-22 y over a 140-y period. Crucially, we uncovered a substantial change in the breeding values for this trait, indicating that the change in AFR largely occurred at the genetic level. Moreover, the genetic trend was higher than expected under the effect of random genetic drift alone. Our results show that microevolution can be detectable over relatively few generations in humans and underscore the need for studies of human demography and reproductive ecology to consider the role of evolutionary processes.

The BRCA2 c.9004G>A (E2003K) variant is likely pathogenic and recurs in breast and/or ovarian cancer families of French Canadian descent

Specific BRCA1 and BRCA2 mutations recur in French Canadian breast and/or ovarian cancer families because of common ancestors, facilitating carrier detection in this population. We recently reported a BRCA2 c.9004G>A variant of unknown clinical significance in two French Canadian breast cancer families. It confers a E3002K alteration in the conserved C-terminus domain of BRCA2, and has been reported in non-French Canadian cancer families. Seven variant positive French Canadian families have since been identified by mutation screening of referrals to hereditary cancer clinics. In this article, we describe the cancer phenotypes of these families and further assess the contribution of this variant in the French Canadian population. We screened index breast cancer cases from 58 cancer families with at least three confirmed cases of breast and/or ovarian cancer and 960 breast cancer cases (48 years mean age) not selected for family history of cancer that were previously found not to carry the most common BRCA1 and BRCA2 mutations reported in this population. The index variant-positive cases from each family had breast cancer between the ages of 35-55 years (43 years mean age); and reported close relatives with breast cancer diagnoses between the ages of 28-84 years (57 years mean age). Three families had ovarian or peritoneal cancers. BRCA2-associated cancers, such as bladder, esophagus, pancreas, prostate, and thyroid cancers also occurred in these families. One c.9004G>A carrier also harbored the PALB2 c.2323C>T (Q775X) mutation found to recur in French Canadian breast cancer cases. No new BRCA2 variant carriers were identified in mutation screens. The absence of BRCA2 c.9004G>A carriers in the breast cancer cases not selected for family history contrasts with familial cases, supporting a pathogenic status for this variant and addition to the existing common BRCA1 and BRCA2 mutation-screening panel for French Canadian breast and/or ovarian cancer families.

Dental age assessment of southern Chinese using the United Kingdom Caucasian reference dataset

Dental age assessment is one the most accurate methods for estimating the age of an unknown person. Demirjian's dataset on a French-Canadian population has been widely tested for its applicability on various ethnic groups including southern Chinese. Following inaccurate results from these studies, investigators are now confronted with using alternate datasets for comparison. Testing the applicability of other reliable datasets which result in accurate findings might limit the need to develop population specific standards. Recently, a Reference Data Set (RDS) similar to the Demirjian was prepared in the United Kingdom (UK) and has been subsequently validated. The advantages of the UK Caucasian RDS includes versatility from including both the maxillary and mandibular dentitions, involvement of a wide age group of subjects for evaluation and the possibility of precise age estimation with the mathematical technique of meta-analysis. The aim of this study was to evaluate the applicability of the United Kingdom Caucasian RDS on southern Chinese subjects. Dental panoramic tomographs (DPT) of 266 subjects (133 males and 133 females) aged 2-21 years that were previously taken for clinical diagnostic purposes were selected and scored by a single calibrated examiner based on Demirjian's classification of tooth developmental stages (A-H). The ages corresponding to each stage of tooth developmental stage were obtained from the UK dataset. Intra-examiner reproducibility was tested and the Cohen kappa (0.88) showed that the level of agreement was 'almost perfect'. The estimated dental age was then compared with the chronological age using a paired t-test, with statistical significance set at p<0.01. The results showed that the UK dataset, underestimated the age of southern Chinese subjects by 0.24 years but the results were not statistically significant. In conclusion, the UK Caucasian RDS may not be suitable for estimating the age of southern Chinese subjects and there is a need for an ethnic specific reference dataset for southern Chinese.

Design and rationale of a genetic cohort study on congenital cardiac disease: experiences from a multi-institutional platform in Quebec

Congenital cardiac disease is the most common malformation, and a substantial source of mortality and morbidity in children and young adults. A role for genetic factors is recognised for these malformations, but overall few predisposing loci have been identified. Here we report the rationale, design, and first results of a multi-institutional congenital cardiac disease cohort, assembled mainly from the French-Canadian population of the province of Quebec and centred on families with multiple affected members afflicted by cardiac malformations. Families were recruited into the study, phenotyped and sampled for DNA in cardiology clinics over the first 3 years of enrolment. We performed segregation analysis and linkage simulations in the subgroup of families with left ventricular outflow tract obstruction (LVOTO). A total of 1603 participants from 300 families were recruited, with 169 out of 300 (56.3%) families having more than one affected member. For the LVOTO group, we estimate heritability to be 0.46-0.52 in our cohort. Simulation analysis demonstrated sufficient power to carry out linkage analyses, with an expected mean log-of-odds (LOD) score of 3.8 in 67 pedigrees with LVOTO. We show feasibility and usefulness of a population-based biobank for genetic investigations into the causes of congenital cardiac disease. Heritability of LVOTO is high and could be accounted for by multiple loci. This platform is ideally suited for multiple analysis approaches, including linkage analysis and novel gene sequencing approaches, and will allow to establish segregation of risk alleles at family and population levels.

Association of Long ATXN2 CAG Repeat Sizes With Increased Risk of Amyotrophic Lateral Sclerosis

To analyze the ataxin 2 (ATXN2) CAG repeat size in a cohort of patients with amyotrophic lateral sclerosis (ALS) and healthy controls. Large (CAG)(n) alleles of the ATXN2 gene (27-33 repeats) were recently reported to be associated with an increased risk of ALS. Case-control study. France and Quebec, Canada. A total of 556 case patients with ALS and 471 healthy controls; both groups of participants are of French or French-Canadian origin. We observed a significant association between ATXN2 high-length alleles (≥29 CAG repeats) and ALS in French and French-Canadian ALS populations. Furthermore, we identified spinocerebellar ataxia type 2-pathogenic polyglutamine expansions (≥32 CAG repeats) in both familial and sporadic ALS cases. Altogether, our findings support ATXN2 high-length repeats as a risk factor for ALS and further indicate a genetic link between spinocerebellar ataxia type 2 and ALS.

LINGO1 Variants in the French-Canadian Population

Essential tremor (ET) is a complex genetic disorder for which no causative gene has been found. Recently, a genome-wide association study reported that two variants in the LINGO1 locus were associated to this disease. The aim of the present study was to test if this specific association could be replicated using a French-Canadian cohort of 259 ET patients and 479 ethnically matched controls. Our genotyping results lead us to conclude that no association exists between the key variant rs9652490 and ET (Pcorr = 1.00).

Prevalence of the Pro12Ala missense mutation in the PPARG2 gene in Kuwaiti patients with primary knee osteoarthritis

BACKGROUND AND OBJECTIVES:Peroxisome proliferator–activated receptors (PPARs) play an important role in a number of cellular and metabolic functions. This study was carried out to determine the prevalence of a missense mutation (Pro12Ala) in the PPARG2 gene in Kuwaiti Arab patients with primary knee osteoarthritis (OA) and healthy controls with the aim of identifying a possible association.DESIGN AND SETTING:A prospective cross-sectional study carried out at three major teaching hospitals (referral centers) in the country over a one-year period.PATIENTS AND METHODS:The prevalence of PPARG2 gene Pro12Ala missense mutation was determined in 104 Kuwaiti Arab patients with primary knee OA and 111 ethnically matched healthy controls. The prevalence of this Pro12Ala missense mutation was also determined in clinical subgroups of OA patients divided on the basis of age at onset, function and radiologic grading.RESULTSThe Pro-Pro genotype of the PPARG2 gene Pro12Ala missense mutation was detected in 95/104 (91.3%) cases compared to 111/111 (100%) in the control subjects. The heterozygous Pro-Ala genotype was detected in 9/104 (8.7%) of the OA patients, while it was not detected in any of the controls. The Ala-Ala genotype was not detected in any of the OA patients or the controls. No significant differences were detected in the PPARG2 gene Pro12Ala genotypes in the subgroups of patients classified on the basis of age at onset, functional assessment using Lequesne’s functional index, and radiological grading using Kellgren-Lawrence (K-L) grading.CONCLUSIONSThis study found no significant association between the PPARG2 gene Pro12Ala missense mutation and knee OA. However, the presence of the Pro-Pro genotype of the PPARG2 gene mutation has a protective effect against development of OA.

French Canadian Cross-Cultural Adaptation of the Developmental Coordination Disorder Questionnaire '07: DCDQ-FC

Parent-report measures, such as the Developmental Coordination Disorder Questionnaire'07 (DCDQ'07), are used to identify developmental coordination disorder (DCD) in children. Early identification of this condition is important to mitigate its social-emotional and health consequences. Unfortunately, few French-language assessments are available to therapists working with francophone populations. The aim of this study was to undertake a formal translation of the English DCDQ'07 and begin to examine its psychometric properties. The translation was done using Beaton, Bombardier, and Guillemin's (2000) guidelines for cross-cultural adaptation. Methodologies described by Haccoun (1987) and Vallerand (1989) were used to address the psychometric qualities of the translation. The DCDQ'07 and its French translation (DCDQ-FC) are equivalent, with excellent internal consistency and test-retest reliability. Concurrent and construct validity were adequate for a screening measure; however, low sensitivity was obtained with both measures. The DCDQ-FC is a valid translation for use with a French Canadian population.

292 Multiple layers of genetic factors interact in the pathogenesis of left ventricular outflow tract obstruction at population level

Left ventricular outflow tract obstruction (LVOTO) is a wide spectrum of congenital heart defects ranging from bicuspid aortic valve to hypoplastic left heart syndrome. Increasing knowledge suggests a strong contribution of genetic factors in this disease spectrum. We have recruited a large cohort of multiplex families with LVOTO. All individuals gave informed consent and underwent physical exam, ECG and echocardiography. We have chosen 45 highly informative families and 23 trios for analysis of linkage and structural genomic variation using high-density genotyping (total cohort n = 450, affected = 217). To confidently call copy number variants, a phenotyped control cohort with 1900 members was used. In the 68 families analyzed to date, only one family with a clear Mendelian segregation pattern was identified. This family exhibits a novel X-linked syndrome with atrial septal defects, aortic valve disease, coarctation and atrial fibrillation. Significant linkage to Xq28 could be demonstrated, with a founder effect in a geographically confined area. In the cohort as a whole, significant linkage to chromosome 6q24 was found, defining an 8 Mb critical interval devoid of any obvious biological candidates and without any founder haplotypes. The analysis of copy number variants reveals 33 candidate loci in a highly complex pattern of inherited and de novo variants, 2/3 of which are gains. We provide a comprehensive high-density scan of LVOTO and identify linkage to two novel candidate loci in the French-Canadian population. Detailed haplotype analyses show conservation in a subset of families. Several layers of genetic factors most likely co-exist within this cohort, with structural genomic variation explaining the majority of phenotypic variability. These results pave the way towards a better definition of the causal genes and gene-gene interactions in LVOTO.

HNF4 alpha: A New Susceptibility Gene for Crohnʼs Disease?: 2010 Presidential Poster

Purpose: Hepatocyte nuclear factor 4 alpha (HNF4α) is a transcription factor mainly expressed in liver, intestine, kidney and pancreas involved in regulating many metabolic functions. Our recent studies in an experimental knock out model supports its potential implication in the physiopathology underlying IBD. However, little is known regarding its potential involvement in humans with Crohn's disease (CD). The aim of this study was to evaluate the association between HNF4α genetic variants and CD. Methods: The sequencing of the promoter, coding and strategic regions of the HNF4α gene was first carried out in a sample population of 40 French Canadian patients, in order to identify the genetic variants prevalent in our population. Thereafter, the identified polymorphisms were genotyped in an extensive French Canadian cohort including 350 CD patients and 650 controls. Results: Sequencing the HNF4α gene led to the identification of 28 polymorphisms. Genotyping these variants in our cohort revealed that 8 polymorphisms demonstrated significant allelic association with CD. Among these variants, one polymorphism leading to a change in the amino acid sequence of the protein, appears to be highly protective against the risk of developing CD (OR: 0.2546, P<0.00001). Moreover, haplotype analyses revealed that one specific haplotype composed of 8 polymorphisms in high linkage disequilibrium and located in the promoter region is also protective against CD (OR: 0.5097, P<0.0027). Conclusion: In a French Canadian population, several HNF4α genetic variants are associated with CD. Our genetic results further support the hypothesis of a relation between HNF4α and physiopathology underlying CD. This study is the first to demonstrate a relationship between HNF4α genetic variants and CD susceptibility.

Tremor–ataxia with central hypomyelination (TACH) leukodystrophy maps to chromosome 10q22.3–10q23.31

Leukodystrophies are a heterogeneous group of disorders associated with abnormal central nervous system white matter. The clinical features invariably include upper motor neuron signs and developmental regression with or without other neurological manifestations. The objective of this study was to characterize clinically and genetically a new form of childhood-onset leukodystrophy with ataxia and tremor. We recruited seven French-Canadian cases belonging to five families affected by an unknown form of childhood-onset leukodystrophy. Genome-wide scans (GWS) were performed using the Illumina Hap310 or Hap610 Bead Chip to identify regions of shared homozygosity that were further studied for linkage with STS markers. All cases presented between the ages of 1 and 5 years with spasticity along with other upper motor neuron signs, prominent postural tremor, and cerebellar signs. Though motor regression is a constant feature, cognitive functions are relatively preserved, even late in the course of the disease. The higher frequency of founder diseases in the French-Canadian population and the segregation in pedigrees are suggestive of a recessive mode of inheritance. By homozygosity mapping, we established linkage to a 12.6-Mb SNP-haplotyped region on chromosome 10q22.3-10q23.31 (maximum LOD score: 5.47). We describe an autosomal recessive childhood-onset leukodystrophy with ataxia and tremor mapping to a 12.6 Mb interval on chromosome 10q22.3-10q23.31. Identification of the mutated gene will allow precise diagnosis and genetic counseling and shed light on how its perturbed function leads to white matter abnormalities.

No significance of the COMT val 158met polymorphism in restless legs syndrome

The catechol-O-methyltransferase (COMT) val 158met polymorphism, which codes for the substitution of valine (val) by methionine (met) leading to a reduced COMT activity in homo- or heterozygous individuals, is associated with individual pain sensitivity and dopaminergic responses in Parkinson's disease as well as with various chronic painful diseases. Recent investigations support the notion of an alteration of the medial pain pathway as well as of the descending inhibitory control system in restless legs syndrome (RLS), that both involve dopaminergic transmission as well. Thus, the distribution of the COMT val 158met polymorphism was assessed in 298 RLS patients and compared with 135 healthy controls in relation to sex, age of onset and family history. The data revealed no significant differences in the distribution of the COMT val 158met polymorphism in RLS patients compared with the control group, also when the heterozygous and the homozygous group containing the 158met allele were combined. In addition, sex, age of onset and family history were not associated with the COMT val 158met polymorphism in this German population of RLS patients. The present study adds to previous mostly negative investigations on the genetic determination of dopaminergic transmission in RLS, which have – so far – only detected an association of the MAO-A activity and RLS in females in a French-Canadian population. Further investigations assessing the different COMT haplotypes and experimental and clinical parameters are nevertheless warranted.

Functional Variation in the Androgen-Receptor Gene Is Associated With Visceral Adiposity and Blood Pressure in Male Adolescents

Intra-abdominal accumulation of fat is a hallmark of male body-fat distribution and a major risk factor for hypertension. Sympathoactivation may be one of the mechanisms linking intra-abdominal obesity to hypertension. The aim of the present study was to investigate whether a functional variation in the androgen-receptor gene (AR, a variable number of CAG repeats in exon 1) is associated with intra-abdominal adiposity, sympathetic modulation of vasomotor tone, and blood pressure in adolescent boys but not girls. We studied 223 boys and 259 girls (age 12 to 18 years) from a French-Canadian founder population. Intra-abdominal fat and subcutaneous-abdominal fat were quantified with an MRI. Blood pressure was recorded beat-to-beat during an hour-long protocol including physical and mental challenges, and these blood pressure time series were used to assess sympathetic modulation of vasomotor tone by power spectral analysis. The results showed that boys with a "low" versus "intermediate" or "high" CAG-repeat number in AR demonstrated higher intra-abdominal fat (by 28% and 48%, respectively) but not subcutaneous-abdominal fat. These intra-abdominal fat differences remained significant after adjusting for serum levels of sex hormones and subcutaneous-abdominal fat. Furthermore, boys with low versus intermediate or high CAG-repeat numbers also showed higher blood pressure, with the differences being most pronounced during mental stress (8.0 and 8.5 mm Hg, respectively) and higher sympathetic modulation of vasomotor tone. As expected, no such differences were seen among girls. In adolescent boys, low CAG-repeat numbers in AR may be a genetic risk factor for intra-abdominal obesity and hypertension; sympathoactivation may be an underlying link between the 2 conditions.

X chromosome and suicide

Suicide completion rates are significantly higher in males than females in most societies. Although gender differences in suicide rates have been partially explained by environmental and behavioral factors, it is possible that genetic factors, through differential expression between genders, may also help explain gender moderation of suicide risk. This study investigated X-linked genes in suicide completers using a two-step strategy. We first took advantage of the genetic structure of the French-Canadian population and genotyped 722 unrelated French-Canadian male subjects, of whom 333 were suicide completers and 389 were non-suicide controls, using a panel of 37 microsatellite markers spanning the entire X chromosome. Nine haplotype windows and several individual markers were associated with suicide. Significant results aggregated primarily in two regions, one in the long arm and another in the short arm of chromosome X, limited by markers DXS8051 and DXS8102, and DXS1001 and DXS8106, respectively. The second stage of the study investigated differential brain expression of genes mapping to associated regions in Brodmann areas 8/9, 11, 44 and 46, in an independent sample of suicide completers and controls. Six genes within these regions, Rho GTPase-activating protein 6, adaptor-related protein complex 1 sigma 2 subunit, glycoprotein M6B, ribosomal protein S6 kinase 90 kDa polypeptide 3, spermidine/spermine N(1)-acetyltransferase 1 and THO complex 2, were found to be differentially expressed in suicide completers.

INTERGENERATIONAL CONTRACTION OF THE CTG REPEATS IN 2 FAMILIES WITH MYOTONIC DYSTROPHY TYPE 1

Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder caused by the expansion of an unstable CTG trinucleotide repeat at chromosome region 19q13.3.1 The number of CTG repeats is unstable in the abnormal range and usually increases in size in successive generations, in association with anticipation.2,3 A decrease in the CTG repeat size during transmission from parents to child can also occur in about 6.4% of transmissions, most frequently during paternal transmissions (10%).4 In the French-Canadian DM1 population, intergenerational contractions occur in about 7.4% of transmissions, all in cases of paternal transmission. We report here 2 French-Canadian DM1 families with paternal transmission, both originating from the Saguenay-Lac St-Jean, in which all affected children display CTG contractions. Although it was already reported that intergenerational contractions could be observed in several sibs in a same family, it was not noted whether this occurred in all affected sibs.4 Overall, these observations support the existence of a paternal factor that prevents CTG expansion. ### Case reports. The pedigree of the 2 families and Southern blot analysis are shown in the figure. Figure Family tree and Southern blot Pedigree of family (A, B). (C, D) Southern blot analysis. The DNA (3–5 μg) was …

Analysis ofDPP6andFGGYas candidate genes for amyotrophic lateral sclerosis

DPP6 and FGGY genes have been recently associated with an increased susceptibility for sporadic amyotrophic lateral sclerosis. Here, we evaluated the role of these genes in ALS pathogenesis by undertaking a sequence analysis of a cohort of 190 ALS patients from France and Quebec. We did not observe any evidence that mutations in DPP6 and FGGY genes are involved in ALS. Our data indicate that mutations in these genes are unlikely to be a common cause of ALS in the French and French Canadian populations.