Global Meta-Analysis on the Association between Behcet Syndrome and Polymorphisms from the HLA Class I (A, B, and C) and Class II (DRB1, DQB1, and DPB1) Genes

Behcet syndrome (BS) is a multisystemic perivasculitis whose genetic susceptibility is linked to HLA region. We first meta-analysed all HLA class I and II genes involved in BS susceptibility in all ethnic groups worldwide. We identified 1141 articles and finally included 31 case-control studies after multiple rounds of selection. We analysed frequencies for 24 HLA-A alleles (3 alleles for HLA-A ∗ 26 at four digits), 50 HLA-B alleles (11 alleles for HLA-B ∗ 51 at four digits), 15 HLA-C alleles, 16 HLA-DRB1 alleles, 6 HLA-DQB1 alleles, and 15 HLA-DPB1 alleles. We meta-analysed only HLA allelic frequencies from at least three studies; therefore, we investigated 21 alleles out of 140. Going from 7.00 to 1.6 OR, we found 11 class I alleles conferring risk for BS: B ∗ 51 : 08 , B ∗ 51 , B ∗ 51 : 01 , B ∗ 51 : 02 , DQB 1 ∗ 03 , A ∗ 26 : 01 , Cw ∗ 14 , Cw ∗ 15 , Cw ∗ 16 , B ∗ 15 , and A ∗ 26 . Overall, the studies included populations from Europe (Greece, Spain, Italy, Germany, and Ireland), Asia (Korea, China, China Han, and Thailand), Middle East (Israel, Saudi Arabia, and Iran), and Morocco (as no other North-African population was included). We collected a number of ethnical groups sufficient to conduct an ethnic-specific meta-analysis where Europeans showed 11.25 OR for B ∗ 51:08 and Japan 3.50 OR for A ∗ 26 : 01 . A remarkable result was that the most frequent HLA − B ∗ 51 two-digit alleles associated with BS were different among populations: HLA − B ∗ 51 : 08 in Europe, HLA − B ∗ 51 : 01 in Turkey, and HLA − B ∗ 51 : 02 in Japan. Overall, we discussed our real-world results with other imputation studies.

Anthropometric Measurements of Non-arthritic Knees in a North African Population, An MRI based Study.

Background: Knee anthropometric characteristics were evaluated for different ethnicities; however, data from North African populations are deficient. The primary aim was to investigate the Egyptian knees' anthropometric characteristics as a representative of North African populations. Secondary aims: 1) to study the anthropometric gender difference, 2) to compare results with other ethnic groups, and 3) to study the mismatch in comparison to geometric characteristics of modern TKA implant designs. Methods: 200 normal knee MRI scans (100 females and 100 males, aging from 18 to 60) were obtained for analysis. Linear measurements (Anteroposterior (AP), Mediolateral (ML), and Aspect ratio (AR)) of the planned cut surface of the distal femur (f) and the proximal tibia (t) were evaluated. Results: A significant difference between both sexes was found, males had larger measurements in anteroposterior [fAP: 60.97 ± 3.1 vs 54.78 ± 3.3 (P < 0.001), tAP: 46.89 ± 3.0 vs 41.35 ± 2.9 (P < 0.001)] and mediolateral [fML: 74.89 ± 3.2 vs 67.29 ± 3.7 (P < 0.001), tML: 76.01 ± 3.0 vs 67.26 ± 3.2 (P < 0.001)], the mean femoral and tibial AP and ML measurements were different from other ethnic groups. None of the seven studied TKA systems matched the largest ML or the smallest AP dimensions of the distal femur in the current study population. Conclusion: A significant difference was found between males' and females' knee anthropometric characteristics. Some of the commonly used TKA implants in our area could not provide a perfect fit and coverage.Trial registration: Clinical Trials .gov identifier: NCT03622034, registered July 28, 2018, (https://clinicaltrials.gov/ct2/show/record/NCT03622034).

Epidemiology of heart failure and long-term follow-up outcomes in a north-African population: Results from the NAtional TUnisian REgistry of Heart Failure (NATURE-HF)

The NATURE-HF registry was aimed to describe clinical epidemiology and 1-year outcomes of outpatients and inpatients with heart failure (HF). This is a prospective, multicenter, observational survey conducted in Tunisian Cardiology centers. A total of 2040 patients were included in the study. Of these, 1632 (80%) were outpatients with chronic HF (CHF). The mean hospital stay was 8.7 ± 8.2 days. The mortality rate during the initial hospitalization event for AHF was 7.4%. The all-cause 1-year mortality rate was 22.8% among AHF patients and 10.6% among CHF patients. Among CHF patients, the older age, diabetes, anemia, reduced EF, ischemic etiology, residual congestion and the absence of ACEI/ ARBs treatment were independent predictors of 1-year cumulative rates of rehospitalization and mortality. The female sex and the functional status were independent predictors of 1-year all-cause mortality and rehospitalization in AHF patients. This study confirmed that acute HF is still associated with a poor prognosis, while the mid-term outcomes in patients with chronic HF seems to be improved. Some differences across countries may be due to different clinical characteristics and differences in healthcare systems.

First Characterization of Congenital Myasthenic Syndrome Type 5 in North Africa

Congenital myasthenic syndromes (CMS) are associated with defects in the structure and the function of neuromuscular junctions. These rare disorders can result from mutations in the collagenic tail of endplate acetylcholinesterase (COLQ) essentially associated with autosomal recessive inheritance.With the lowered cost of genetic testing and increased access to next-generation sequencing, many mutations have been reported to date. In this study we identified the first COLQ homozygous mutation c.1193T>A in the North African population. This study outlines the genetic and phenotypic features of a CMS patient in a Moroccan family. It also describes a novel COLQ missense mutation associated with CMS-5. COLQ mutations are probably underdiagnosed in these North African populations, this is an issue as CMS-5 may be treated with ephedrine, and albuterol. Indeed, patients can seriously benefit and even recover after the treatment that should be planned according to genetic tests and clinical findings.

Identification and Characterization of the Most Common Genetic Variant Responsible for Acephalic Spermatozoa Syndrome in Men Originating from North Africa

Acephalic spermatozoa syndrome (ASS) is a rare but extremely severe type of teratozoospermia, defined by the presence of a majority of headless flagella and a minority of tail-less sperm heads in the ejaculate. Like the other severe monomorphic teratozoospermias, ASS has a strong genetic basis and is most often caused by bi-allelic variants in SUN5 (Sad1 and UNC84 domain-containing 5). Using whole exome sequencing (WES), we investigated a cohort of nine infertile subjects displaying ASS. These subjects were recruited in three centers located in France and Tunisia, but all originated from North Africa. Sperm from subjects carrying candidate genetic variants were subjected to immunofluorescence analysis and transmission electron microscopy. Moreover, fluorescent in situ hybridization (FISH) was performed on sperm nuclei to assess their chromosomal content. Variant filtering permitted us to identify the same SUN5 homozygous frameshift variant (c.211+1_211+2dup) in 7/9 individuals (78%). SUN5 encodes a protein localized on the posterior part of the nuclear envelope that is necessary for the attachment of the tail to the sperm head. Immunofluorescence assays performed on sperm cells from three mutated subjects revealed a total absence of SUN5, thus demonstrating the deleterious impact of the identified variant on protein expression. Transmission electron microscopy showed a conserved flagellar structure and a slightly decondensed chromatin. FISH did not highlight a higher rate of chromosome aneuploidy in spermatozoa from SUN5 patients compared to controls, indicating that intra-cytoplasmic sperm injection (ICSI) can be proposed for patients carrying the c.211+1_211+2dup variant. These results suggest that the identified SUN5 variant is the main cause of ASS in the North African population. Consequently, a simple and inexpensive genotyping of the 211+1_211+2dup variant could be beneficial for affected men of North African origin before resorting to more exhaustive genetic analyses.

SLC22A4 Gene in Hereditary Non-syndromic Hearing Loss: Recurrence and Incomplete Penetrance of the p.C113Y Mutation in Northwest Africa

Inherited hearing loss is extremely heterogeneous both clinically and genetically. In addition, the spectrum of deafness-causing genetic variants differs greatly among geographical areas and ethnicities. The identification of the causal mutation in affected families allows early diagnosis, clinical follow-up, and genetic counseling. A large consanguineous family of Moroccan origin affected by autosomal recessive sensorineural hearing loss (ARSNHL) was subjected to genome-wide linkage analysis and exome sequencing. Exome-wide variant analysis and prioritization identified the SLC22A4 p.C113Y missense variant (rs768484124) as the most likely cause of ARSNHL in the family, falling within the unique significant (LOD score&gt;3) linkage region on chromosome 5. Indeed, the same variant was previously reported in two Tunisian ARSNHL pedigrees. The variant is present in the homozygous state in all six affected individuals, but also in one normal-hearing sibling, suggesting incomplete penetrance. The mutation is absent in about 1,000 individuals from the Greater Middle East Variome study cohort, including individuals from the North African population, as well as in an additional seven deaf patients from the same geographical area, recruited and screened for mutations in the SLC22A4 gene. This study represents the first independent replication of the involvement of SLC22A4 in ARSNHL, highlighting the importance of the gene, and of the p.C113Y mutation, at least in the Northwest African population.