Consanguinity and Inbreeding in Health and Disease in North African Populations.

North Africa is defined as the geographical region separated from the rest of the continent by the Sahara and from Europe by the Mediterranean Sea. The main demographic features of North African populations are their familial structure and high rates of familial and geographic endogamy, which have a proven impact on health, particularly the occurrence of genetic diseases, with a greater effect on the frequency and spectrum of the rarest forms of autosomal recessive genetic diseases. More than 500 different genetic diseases have been reported in this region, most of which are autosomal recessive. During the last few decades, there has been great interest in the molecular investigation of large consanguineous North African families. The development of local capacities has brought a substantial improvement in the molecular characterization of these diseases, but the genetic bases of half of them remain unknown. Diseases of known molecular etiology are characterized by their genetic and mutational heterogeneity, although some founder mutations are encountered relatively frequently. Some founder mutations are specific to a single country or a specific ethnic or geographic group, and others are shared by all North African countries or worldwide. The impact of consanguinity on common multifactorial diseases is less evident.

Surveillance for variant CJD: should more children with neurodegenerative diseases have autopsies?

OBJECTIVES: To report investigations performed in children with progressive neurodegenerative diseases reported to this UK study. DESIGN: Since 1997 paediatric surveillance for variant Creutzfeldt-Jakob disease (vCJD) has been performed by identifying children aged less than 16 years with progressive intellectual and neurological deterioration (PIND) and searching for vCJD among them. SETTING: The PIND Study obtains case details from paediatricians who notify via the British Paediatric Surveillance Unit. PARTICIPANTS: Between May 1997 and October 2017, a total of 2050 cases meeting PIND criteria had been notified and investigated. RESULTS: Six children had vCJD. 1819 children had other diagnoses, made in 12 cases by antemortem brain biopsy and in 15 by postmortem investigations. 225 children were undiagnosed: only 3 had antemortem brain biopsies and only 14 of the 108 who died were known to have had autopsies; postmortem neuropathological studies were carried out in just 10% (11/108) and only two had prion protein staining of brain tissue. Of the undiagnosed cases 43% were known to come from Asian British families. CONCLUSIONS: Most of the notified children had a diagnosis other than vCJD to explain their neurological deterioration. None of the undiagnosed cases had the clinical phenotype of vCJD but brain tissue was rarely studied to exclude vCJD. Clinical surveillance via the PIND Study remains the only practical means of searching for vCJD in UK children.

Non-musculoskeletal benefits of vitamin D.

The aim of this study is to determine and critically evaluate the plausible relationships of vitamin D with extra-skeletal tissues in humans. Severe vitamin D deficiency results in rickets in children and osteomalacia in adults; these beneficial effects in the musculoskeletal system and certain physiological functions are well understood. Nevertheless, mounting reports support additional beneficial effects of vitamin D, outside the musculoskeletal system. This review explores the recent advances in knowledge about the non-skeletal effects of vitamin D. Peer-reviewed papers were extracted from research databases using key words, to assess correlations between vitamin D and extra-skeletal diseases and conditions. As per the guidelines of the Preferred Reporting Items for Systematic Reviews (PRISMA); general interpretations of results are included; taking into consideration the broader evidence and implications. This review summarizes current knowledge of the effects of vitamin D status on extra-skeletal tissues with special attention given to relationships between vitamin D status and various diseases commonly affecting adults; the effects of intervention with vitamin D and exposure to sunlight. Evidence suggests that vitamin D facilitates the regulation of blood pressure; and cardiac; endothelial; and smooth muscle cell functions; playing an important role in cardiovascular protection. In addition; 1,25(OH)2D improves immunity; subdues inflammation; and reduces the incidence and severity of common cancers; autoimmune diseases and infectious diseases. Almost all adequately powered; epidemiological and biological studies that use; adequate doses of vitamin D supplementation in D-deficient populations have reported favorable outcomes. These studies have concluded that optimizing 25(OH)D status improves the functionality of bodily systems; reduces comorbidities; improves the quality of life; and increases survival. Although accumulating evidence supports biological associations of vitamin D sufficiency with improved physical and mental functions; no definitive evidence exists from well-designed; statistically powered; randomized controlled clinical trials. Nevertheless, most studies point to significant protective effects of vitamin D in humans when the minimum 25(OH)D serum level exceeds 30ng/mL and is maintained throughout the year.

Analysis of the CTAGE5 P521A variation with the risk of familial idiopathic basal ganglia calcification in an Iranian population.

Familial idiopathic basal ganglia calcification (IBGC) is a rare neurodegenerative syndrome with an autosomal dominant pattern of inheritance which is characterized by deposition of calcium in the basal ganglia and other brain regions. Linkage studies demonstrated its genetic heterogeneity; however, the responsible genes are unknown. Recently, a heterozygous variation (C>G, P521A) at exon 20 of the human cutaneous T cell lymphoma-associated antigen 5 (CTAGE5) gene was found in all patients of the affected large American family linked to IBGC1 (14q11.2-21.3). However, no carrier was detected in the two affected Brazilian families. This study was performed to investigate whether the CTAGE5 P521A variation is associated with the IBGC in an affected Iranian family. Genotyping of the CTAGE5 P521A variation was determined using PCR-RFLP. Totally, 22 members of an affected Iranian family as well as 100 normal people as control group were screened. All the samples including 22 members of the affected family as well as all control people had normal CC genotype and no GC carrier was found. Our result is similar to a Brazilian study but contrary to an American report, strengthening genetic heterogeneity of this syndrome. It seems that additional studies are necessary to confirm the pathogenicity of this rare mutation.

Comparison of 24-h volume and creatinine-corrected total urinary polyphenol as a biomarker of total dietary polyphenols in the Invecchiare InCHIANTI study.

Polyphenols have beneficial effects on several chronic diseases but assessing polyphenols intake from self-reported dietary questionnaires tends to be inaccurate and not very reliable. A promising alternative is to use urinary excretion of polyphenols as a proxy measure of intake. The best method to assess urinary excretion is to collect 24-h urine. However, since collecting 24-h urine method is expensive, time consuming and may be difficult to implement in large population-based studies, measures obtained from spot urine normalized by creatinine are commonly used. The purpose of the study was to evaluate the correlation between polyphenols dietary intake and total urinary polyphenol excretion (TPE), expressed by both 24-h volume and urinary creatinine normalization in 928 participants from the InCHIANTI study. Dietary intake data were collected using a validated food frequency questionnaire. Urinary TPE was analyzed by Folin-Ciocalteau assay. Both urinary TPE expression models were statistically correlated (r=0.580), and the partial correlation coefficient improved (pr=0.722) after adjusting for the variables that modify the urinary creatinine excretion (i.e. gender, age, BMI, physical activity and renal function). In crude models, polyphenol intake was associated with TPE corrected by 24-h volume (r=0.211; P<0.001), but not with creatinine normalization (r=0.014; P=0.692). However, urinary TPE expressed by creatinine correction was significantly correlated with dietary polyphenols after adjusting for covariates (pr=0.113; P=0.002). We conclude that urinary TPE expressed by 24-h volume is a better biomarker of polyphenol dietary intake than by urinary creatinine normalization. After covariate adjustment, both can be used for studying the relationships between polyphenol intake and health in large-scale epidemiological studies.