Chromosomal abnormalities in 163 Tunisian couples with recurrent miscarriages

Recurrent miscarriage (RM) is defined as three or more consecutive pregnancy losses before 24 weeks of gestation. Parental chromosomal abnormalities represent an important etiology of RM. The aim of the present study was to identify the distribution of chromosome abnormalities among Tunisian couples with RM referred to the Department of Cytogenetic at the Pasteur Institute of Tunis (Tunisia) during the last five years. Standard cytogenetic analysis was carried out in a total of 163 couples presenting with two or more spontaneous abortions. Karyotypes were analyzed by R-banding. We identified 14 chromosomal abnormalities including autosomal reciprocal translocation, Robertsonian translocation, inversion, mosaic aneuploidy and heteromorphysm. The overall prevalence of chromosomal abnormalities was 8.5% in our cohort. This finding underlies the importance of cytogenetic investigations in the routine management of RM

Interaction of Mitochondrial Polygenic Score and Lifestyle Factors in LRRK2 p.Gly2019Ser Parkinsonism.

peer reviewed[en] BACKGROUND: A mitochondrial polygenic score (MGS) is composed of genes related to mitochondrial function and found to be associated with Parkinson's disease (PD) risk. OBJECTIVE: To investigate the impact of the MGS and lifestyle/environment on age at onset (AAO) in LRRK2 p.Gly2019Ser parkinsonism (LRRK2-PD) and idiopathic PD (iPD). METHODS: We included N = 486 patients with LRRK2-PD and N = 9259 with iPD from the Accelerating Medicines Partnership® Parkinson's Disease Knowledge Platform (AMP-PD), Fox Insight, and a Tunisian Arab-Berber founder population. Genotyping data were used to perform the MGS analysis. Additionally, lifestyle/environmental data were obtained from the PD Risk Factor Questionnaire (PD-RFQ). Linear regression models were used to assess the relationship between MGS, lifestyle/environment, and AAO. RESULTS: Our derived MGS was significantly higher in PD cases compared with controls (P = 1.1 × 10-8 ). We observed that higher MGS was significantly associated with earlier AAO in LRRK2-PD (P = 0.047, β = -1.40) and there was the same trend with a smaller effect size in iPD (P = 0.231, β = 0.22). There was a correlation between MGS and AAO in LRRK2-PD patients of European descent (P = 0.049, r = -0.12) that was visibly less pronounced in Tunisians (P = 0.449, r = -0.05). We found that the MGS interacted with caffeinated soda consumption (P = 0.003, β = -5.65) in LRRK2-PD and with tobacco use (P = 0.010, β = 1.32) in iPD. Thus, patients with a high MGS had an earlier AAO only if they consumed caffeinated soda or were non-smokers. CONCLUSIONS: The MGS was more strongly associated with earlier AAO in LRRK2-PD compared with iPD. Caffeinated soda consumption or tobacco use interacted with MGS to predict AAO. Our study suggests gene-environment interactions as modifiers of AAO in LRRK2-PD

Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

An unusual pigmented skin lesion on the nipple‐areola area

Abstract Considering the rarity and underdiagnoses of this disorder, a pigmented and hyperkeratotic skin lesion located on the trunk, resembling to acanthosis nigricans should always be investigated for terra firma‐forme dermatosis (TFFD) and thus alcohol must be applied. TFFD should be known among dermatologists and can be easily diagnosed and treated with isopropyl alcohol

The relationship between alopecia areata and alexithymia, anxiety and depression: A case-control study

Background: Alopecia areata (AA) is a skin disease characterized by the sudden appearance of areas of hair loss on the scalp and other hair-bearing areas, but its aesthetic repercussions can lead to profound changes in patient′s psychological status and relationships. Aim: The goal was to investigate a possible relationship between AA and alexithymia as well as two other emotional dimensions, anxiety and depression. Materials and Methods: Fifty patients with AA seen in the Department of Dermatology of Hedi Chaker University Hospital, Sfax were included in this study. Anxiety and depression were evaluated by Hospital Anxiety and Depression scale questionnaire, alexithymia was assessed by Toronto Alexithymia scale 20, and severity of AA was measured by Severity of Alopecia Tool. Results: Patient′s mean age was 32.92 years. 52% of patients were females. Depression and anxiety were detected respectively in 38% and 62% of patients. There was statistically significant difference between patients and control group in terms of depression (P = 0.047) and anxiety (P = 0.005). Forty-two percent of patients scored positive for alexithymia. No significant difference was found between patient and control groups (P = 0.683) in terms of alexithymia. Anxiety was responsible for 14.7% of variation in alexithymia (P = 0.047). Conclusions: Our study shows a high prevalence of anxiety and depressive symptoms in AA patients. Dermatologists should be aware of the psychological impact of AA, especially as current treatments have limited effectiveness

Lichenoid lesions around the anus: An unusual site of Hailey–Hailey disease

Abstract The anal region is an unusual site of Hailey–Hailey disease. It manifests with lichenoid lesions with crusted erosions around the anus. It should be differentiated from condylomata acuminata, extramammary Paget disease, and bowenoid papulosis

Unilateral hyperpigmented lesion of the breast

Abstract Muco‐cutaneous melanosis is a benign entity with no progression. Although, dermoscopic features may help to differentiate melanosis from malignant pigmented diseases, histopathology remains crucial for the confirming of melanosis of the nipple and areola. Herein, we represent a new case of melanosis of the areola and we describe its clinico‐pathological aspects

Quality of Life in Alopecia Areata: A Sample of Tunisian Patients

Background. Alopecia areata (AA) has a significant impact on the quality of life and social interaction of those suffering from it. Our aim was to assess the impact of AA on the quality of life. Methods. Fifty patients diagnosed with AA seen in the Department of Dermatology of Hedi Chaker University Hospital, between March 2010 and July 2010, were included. Quality of life was measured by SF 36; severity of AA was measured by SALT. Results. Eighty percent had patchy alopecia with less than 50% involvement, 12% had patchy alopecia with 50–99% involvement, and 8% had alopecia totalis. Compared with the general population, AA patients presented a significantly altered quality of life, found in the global score and in five subscores of the SF-36: mental health, role emotional, social functioning, vitality, and general health. Gender, age, marital status, and severity of alopecia areata had a significant influence on patients’ quality of life. Conclusions. This study indicates that patients with AA experience a poor quality of life, which impacts their overall health. We suggest screening for psychiatric distress. Studies of interventions such as counseling, psychoeducation, and psychotherapeutic interventions to reduce the impact of the disease may be warranted

A Tunisian patient with CLCN2‐related leukoencephalopathy

Abstract CLCN2‐related leukoencephalopathy (CC2L OMIM#: 615651) is a recently identified rare disorder. It is caused by autosomal recessive mutations in the CLCN2 gene and leads to the dysfunction of its encoded CLC‐2 chloride channel protein with characteristic brain MRI features of leukoencephalopathy. We report the first Tunisian patient with clinical features of ClCN‐2‐related leukoencephalopathy. A 54‐year‐old female with a family history of leukemia, male infertility, motor disability, and headaches who initially presented with a tension‐type headache and normal physical examination. At the follow‐up, she developed mild gait ataxia and psycho‐cognitive disturbances. A previously reported homozygous NM_004366.6(CLCN2):c.1709G > A (p.Trp570Ter) stop gained mutation was identified. This report expands the knowledge related to CC2L and highlights the clinical features in affected individuals of African descent