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Confined placental mosaicism (CPM) is thought to be one of the main sources of false-positive prenatal cell-free DNA (cfDNA) screening results, but extensive and systematic studies to prove this statement are limited. We evaluate the contribution of CPM to false-positive prenatal cfDNA screening results in the largest cohort published to date. We systematically offered postnatal analysis on placenta and umbilical cord to women who had a negative amniocentesis following a positive prenatal cfDNA screening result. A standardized protocol was used in which (when available) biopsies were taken at five locations in the placenta and umbilical cord. We analyzed a series of 99 placentas. CPM could be confirmed in 32.3 % of cases (32/99). CPM was detected across all subtypes of chromosomal aberrations (common and rare autosomal trisomies, sex chromosome abnormalities, copy number variations and autosomal monosomies). A lower detection rate was present in umbilical cord biopsies in comparison with placental biopsies. When comparing different sections of the placenta, no clear difference could be observed with regard to the probability of CPM being present nor to the grade of mosaicism. We confirm an important role for CPM in explaining false-positive prenatal cfDNA screening results. Placental regional differences are common. Given its limited clinical relevance, we do however not advocate placental studies in a diagnostic setting. • Confined placental mosaicism contributes significantly to discordant prenatal cfDNA screening results. • Placental regional differences are common in confined placental mosaicism. • We do not recommend placental studies in a clinical setting. [ABSTRACT FROM AUTHOR]

Background: Familial aggregation of alopecia areata (AA) has been previously described, but systematic studies with information obtained directly from family members have yet to be undertaken. Objective: We sought to study the pattern of familial aggregation of AA by assessing the affection status of patients'' relatives. The study included 206 index patients with a total of 1029 first-degree and 2625 second-degree relatives. Methods: First-degree relatives were directly interviewed, whereas information on second-degree relatives was obtained by interviewing the index patients and their first-degree relatives. Results: Estimated lifetime risks were 7.1% in siblings, 7.8% in parents, and 5.7% in offspring. The risk in second-degree relatives was slightly higher than the reported population risk. Age at onset in index patients and first-degree relatives was significantly correlated. Limitations: Using patients drawn from specialized hair clinics may have produced results showing a higher proportion of early onset and severe cases. Conclusion: The familial aggregation of AA supports the role of genetic factors in the development of the disease. In addition, our data indicate genetic factors might contribute to the age at onset of AA. [Copyright &y& Elsevier]

Abstract: After their successful introduction in postnatal testing, genome-wide arrays are now rapidly replacing conventional karyotyping in prenatal diagnostics. While previous studies have demonstrated the advantages of this method, we are confronted with difficulties regarding the technology and the ethical dilemmas inherent to genomic arrays. These include indication for testing, array design, interpretation of variants and how to deal with variants of unknown significance and incidental findings. The experiences with these issues reported in the literature are most often from single centres. Here, we report on a national consensus approach how microarray is implemented in all genetic centres in Belgium. These recommendations are subjected to constant re-evaluation based on our growing experience and can serve as a useful tool for those involved in prenatal diagnosis. [Copyright &y& Elsevier]

Recently, the first genome-wide association study (GWAS) of alopecia areata (AA) was conducted in a North-American sample, and this identified eight susceptibility loci surpassing genome-wide significance. The aim of the present follow-up association analysis was to confirm five of these eight loci (single-nucleotide polymorphisms (SNPs) from the CTLA4, IL-2RA, and HLA regions were not included due to previous own findings) and test 12 other loci from the GWAS, which did not surpass the threshold for genome-wide significance. Twenty-three SNPs from the 17 loci were investigated using a sample of 1,702 Central European AA patients and 1,723 controls. Of the five loci with previously reported genome-wide significance, association was confirmed for all of these: ULBP3/ULBP6, PRDX5, IL-2/IL-21, STX17, and IKZF4/ERBB3 (P-value <0.05). To detect robust evidence for association among the 12 other loci, a meta-analysis of the present association data and the data of the recent GWAS was performed. Genome-wide significant association was found for rs20541 (Pcomb=7.52 × 10−10; odds ratio (OR)=1.30 (1.23-1.38)) and rs998592 (Pcomb=1.11 × 10−11; OR=1.28 (1.21-1.36)), thus establishing IL-13 and KIAA0350/CLEC16A as susceptibility loci for AA. Interestingly, IL-13 and KIAA0350/CLEC16A are susceptibility loci for other autoimmune diseases, supporting the hypothesis of shared pathways of autoimmune susceptibility. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the association between the variants of the gene coding for the cytotoxic T lymphocyte antigen-4 (CTLA4) and alopecia areata (AA).

Alopecia areata (AA) is a common dermatological disease, which affects nearly 2% of the general population. Association of AA with atopic disease has been repeatedly reported. Loss-of-function mutations in the filaggrin gene (FLG) may be considered as promising candidates in AA, as they have been observed to be a strong risk factor in atopic dermatitis. The FLG mutations R501X and 2282del4 were genotyped in a large sample of AA patients (n=449) and controls (n=473). Although no significant association was observed in the patient sample overall, FLG mutations were significantly associated with the presence of atopic dermatitis among AA patients. Furthermore, the presence of FLG mutations had a strong impact on the clinical course of AA in comorbid patients. For example, 19 of the 22 mutation carriers among AA patients with atopic dermatitis showed a severe form of the disease (P=0.003; odds ratio (OR)=5.47 (95% confidence interval (CI): 1.59–18.76)). In conclusion, our data suggest that when AA occurs in conjunction with FLG-associated atopic disorder, the clinical presentation of AA may be more severe.Journal of Investigative Dermatology (2007) 127, 2539–2543; doi:10.1038/sj.jid.5700915; published online 21 June 2007 [ABSTRACT FROM AUTHOR]

The article offers information on a study related to common human hair loss disorder alopecia areata (AA). It mentions that the precise etiopathogenesis of AA remains unknown, immunological and genetic association studies have implicated both innate and acquired immunity. It also mentions that immunochip is a unique custom-based Illumina Bead-chip array that enables dense mapping of a large number of susceptibility loci and risk variants for immune-mediated disease.