A recurrent mutation in DEPDC5 predisposes to focal epilepsies in the French-Canadian population.

Familial focal epilepsy with variable foci (FFEVF) is a heterogeneous epilepsy syndrome originally described in the French-Canadian (FC) population. Mutations in DEPDC5 have recently been identified in multiple cases of FFEVF as well as in a wide spectrum of other familial focal epilepsies. In this study, we aimed to determine the frequency of mutation of this gene in our large cohort of FC individuals with FFEVF, as well as familial and sporadic cases with focal epilepsy. We report a recurrent p.R843X protein-truncating mutation segregating in one large FFEVF and two small focal epilepsy FC families. Fine genotyping suggests an ancestral allele. A new p.T864M variant, predicted to be disease-causing, was also identified in a small FC family. Overall, we identified DEPDC5 mutations in 5% of our familial and sporadic focal epilepsy cases (4/79). Our results support the view that mutations in the DEPDC5 gene are an important cause of autosomal dominant focal epilepsies in the FC population, including a founder mutation that is specific to this population. These findings may facilitate molecular diagnosis in clinical practice.

A novel autosomal recessive limb-girdle muscular dystrophy with quadriceps atrophy maps to 11p13-p12.

Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of pathologies. We have identified a cohort of 14 French-Canadian patients from eight different families displaying a novel form of LGMD with an autosomal recessive inheritance. These patients share some features with previously described cases of 'quadriceps myopathy' that evolved into an LGMD. All demonstrate quadriceps femoris asymmetrical atrophy. Creatine kinase values were variable from normal to 6000 U/l. Clinical evaluations and MRI studies demonstrate a variable intrafamilial and interfamilial phenotype. Asymmetrical muscle involvement was clinically observed and confirmed by imaging. MRI studies suggest that the hamstrings and the adductor magnus are the first limb muscles to demonstrate fatty infiltration. Muscle pathology shows no sign of active inflammation but increased endomysial connective tissue associated with basal lamina duplication and collagen disorganization. A genome-wide scan using the two largest families uncovered linkage to marker D11S1360 on chromosome 11p12 [multipoint logarithm of the odds (LOD) score of 2.78]. Further genotyping for the eight families confirmed linkage to this new LGMD locus (multipoint LOD score of 4.56). Fine mapping subsequently defined a less than 3.3 cM candidate interval on 11p13-p12. Haplotype analysis of carrier chromosomes suggests that the most frequent mutation may account for up to 81.3% of French-Canadian mutations. In this study, we describe the chromosomal locus of a new form of recessive LGMD with prominent quadriceps femoris atrophy.

A new autosomal recessive spastic ataxia associated with frequent white matter changes maps to 2q33-34.

Recessive ataxias are a heterogeneous group of diseases. We identified a group of 23 French-Canadian cases belonging to 17 families affected by an autosomal recessive spastic ataxia associated with frequent white matter changes. The fact that 59% of these families have a genealogical relationship to the Portneuf County of Quebec suggests that this is a new form of ataxia with a regional founder effect. All cases present with cerebellar ataxia and spasticity. There is great intrafamilial and interfamilial variability, as illustrated by the spectrum of age of diagnosis (range: 2-59 years, mean: 15.0) and the presence of white matter changes on MRI in 52.4% of cases. The more severe cases have spasticity from birth, scoliosis, dystonia and cognitive impairment and were considered cases of cerebral palsy. Brain MRI constantly shows cerebellar atrophy, which in some cases may be associated with cortical atrophy, leucoencephalopathy and corpus callosum thinning. A genome wide scan uncovered linkage of three families to marker D2S2321 localized on chromosome 2q33-34. Linkage analysis confirmed that all families are linked to the same region [multipoint log of the odds (LOD) score of 5.95]. Haplotype analysis and allele sharing suggest that one common mutation may account for 97% of carrier chromosomes in Quebec. The uncovering of the mutated gene may point to a common pathway for pyramidal and cerebellar degeneration as both are often observed in recessive ataxias and complicated paraplegias.

[Maternal anemia in the southeast and northeast regions of New Brunswick and the impact on hematological parameters and the growth of the newborn]. / Anémie maternelle dans les régions du sud-est et du nord-est du Nouveau-Brunswick et impact sur les paramétres hématologiques et la croissance du nouveau-né.

The prevalence of anaemia remains a major nutritional problem in industrialized countries. The aim of this study was to compare the prevalence of maternal anaemia in southeastern and northeastern areas of New Brunswick and to identify a potential interaction between maternal haematologic indices and the growth, hemoglobin (Hb) and hematocrit (Ht) of newborns. In this retrospective study, 952 obstetric and paediatric records, including 654 from the southeastern area (Greater Moncton) and the rest from the northeastern area (Acadian Peninsula) of New Brunswick, were investigated. The prevalence of maternal anaemia was 21.4% in the Greater Moncton area, compared to 11.5% in the Peninsula. The majority of anaemic women suffered from a light form of anaemia, mainly in the third trimester. Immediately after delivery, 52% of women from Greater Moncton and 40% from the Acadian Peninsula had Hb below normal. A positive correlation was observed between maternal Hb and newborn Hb and between maternal Ht and newborn Hb. Results indicate that maternal anaemia is prevalent in both areas under study and confirm the importance of implementing effective prevention measures.

Early diet influences hepatic hydroxymethyl glutaryl coenzyme A reductase and 7alpha-hydroxylase mRNA but not low-density lipoprotein receptor mRNA during development.

Plasma cholesterol levels increase after birth, and to a greater extent in breast-fed versus formula-fed infants. This increase is believed to be due to the high fat and cholesterol content of the infant diet, but little is known about the effects of early diet on the expression of proteins involved in regulating cholesterol metabolism. This study examined changes in the expression of hepatic proteins regulating cholesterol metabolism during development. Newborn piglets were fed sow milk or one of four formulas for 18 days. The formulas had similar levels of palmitic acid (16:0) as in milk, supplied as palm olein oil with 16:0 esterified predominantly to the sn-1,3 position or as synthesized triglyceride (TG) with 16:0 esterified mainly to the sn-2 position of glycerol, each with no cholesterol (<0.10 mmol/L) or 0.65 mmol/L cholesterol added. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of mRNA levels was used to assess the effects of diet on hepatic hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase, low-density lipoprotein (LDL) receptor, and 7alpha-hydroxylase (C7H). LDL receptor mRNA levels showed no appreciable difference between milk- and formula-fed piglets. However, the levels of HMG-CoA reductase and C7H mRNA were higher (P < .05) in all formula-fed versus milk-fed piglets, irrespective of the formula TG source or cholesterol content. The lower levels of HMG-CoA reductase and C7H mRNA in milk-fed piglets were accompanied by higher (P < .05) plasma total, high-density lipoprotein (HDL), and apolipoprotein (apo) B-containing cholesterol. These studies show that the levels of hepatic HMG-CoA reductase and C7H mRNA, but probably not LDL receptor mRNA, are altered by early diet.

Development of visual acuity in relation to plasma and erythrocyte omega-6 and omega-3 fatty acids in healthy term gestation infants.

The development of preferential looking acuity was studied prospectively to 3 mo of age in exclusively breast-fed and formula-fed term gestation infants. The formula contained (% of total fatty acids) 17.9% linoleic acid (18:2 omega-6) and 2.1% alpha-linolenic acid (18:3 omega-3) but no docosahexaenoic acid (22:6 omega-3) or arachidonic acid (20:4 omega-6). The breast milk contained (mean +/- SEM) 13.4 +/- 0.8% 18:2 omega-6, 1.5 +/- 0.1% 18:3 omega-3, 0.51 +/- 0.03% 20:4 omega-6, and 0.22 +/- 0.02% 22:6 omega-3. Preferential looking acuity, assessed by the acuity-card procedure, and plasma phospholipid and erythrocyte phosphatidylcholine and phosphatidylethanolamine fatty acids were determined at 14 d and 3 mo of age. There were no significant differences in acuity at 14 d or 3 mo, despite substantial differences in erythrocyte and plasma lipid 22:6 omega-3. Visual acuity was [mean (cycles/degree) +/- SD (octaves)] 3.93 +/- 0.54 and 4.77 +/- 0.48 and erythrocyte phosphatidylethanolamine %22:6 omega-3 was (mean +/- SE) 7.6 +/- 0.5 and 4.0 +/- 0.2 in the 3-mo-old breast-fed and formula-fed infants, respectively. These studies show that feeding formula containing 2.1% 18:3 omega-3 (approximately 1.0% energy) results in development of visual acuity similar to breast-feeding in term infants to > or = 3 mo of age.