DNA repair-related heritable photosensitivity syndromes: Mutation landscape in a multiethnic cohort of 17 multigenerational families with high degree of consanguinity.

Inherited photosensitivity syndromes are a heterogeneous group of genetic skin disorders with tremendous phenotypic variability, characterized by photosensitivity and defective DNA repair, especially nucleotide excision repair. A cohort of 17 Iranian families with heritable photosensitivity syndromes was evaluated to identify their genetic defect. The patients' DNA was analyzed with either whole-exome sequencing or RNA sequencing (RNA-Seq). The interpretations of the genomic results were guided by genome-wide homozygosity mapping. Haplotype analysis was performed for cases with recurrent mutations. RNA-Seq, in addition to mutation detection, was also utilized to confirm the pathogenicity. Thirteen sequence variants, including six previously unreported pathogenic variants, were disclosed in 17 Iranian families, with XPC as the most common mutated gene in 10 families (59%). In one patient, RNA-Seq, as a first-tier diagnostic approach, revealed a non-canonical homozygous germline variant: XPC:c.413-9 T > A. The Sashimi plot showed skipping of exon 4 with dramatic XPC down-expression. Haplotype analysis of XPC:c.2251-1 G>C and XPC:1243 C>T in four families showed common haplotypes of 1.7 Mb and 2.6 Mb, respectively, denoting a founder effect. Lastly, two extremely rare cases were presented in this report: a homozygous UVSSA:c .1990 C>T was disclosed, and ERCC2-related cerebro-oculo-facio-skeletal (COFS) syndrome with an early childhood death. A direct comparison of our data with the results of previously reported cohorts demonstrates the international mutation landscape of DNA repair-related photosensitivity disorders, although population-specific differences were observed.

Mutation update: The spectra of PLEC sequence variants and related plectinopathies.

Plectin, encoded by PLEC, is a cytoskeletal linker of intermediate filaments expressed in many cell types. Plectin consists of three main domains that determine its functionality: the N-terminal domain, the Rod domain, and the C-terminal domain. Molecular defects of PLEC correlating with the functional aspects lead to a group of rare heritable disorders, plectinopathies. These multisystem disorders include an autosomal dominant form of epidermolysis bullosa simplex (EBS-Ogna), limb-girdle muscular dystrophy (LGMD), aplasia cutis congenita (ACC), and an autosomal recessive form of EBS, which may associate with muscular dystrophy (EBS-MD), pyloric atresia (EBS-PA), and/or congenital myasthenic syndrome (EBS-MyS). In this study, genotyping of over 600 Iranian patients with epidermolysis bullosa by next-generation sequencing identified 15 patients with disease-causing PLEC variants. This mutation update analyzes the clinical spectrum of PLEC in our cohort and in the literature and demonstrates the relationship between PLEC genotype and phenotypic manifestations. This study has integrated our seven novel PLEC variants and phenotypic findings with previously published data totaling 116 variants to provide the most complete overview of pathogenic PLEC variants and related disorders.

Assessment of health-related quality of life in patients with frontal fibrosing alopecia.

BACKGROUND: Frontal fibrosing alopecia (FFA) is a primary patterned cicatricial alopecia with different manifestations. AIMS: Its incidence is increasing worldwide. Like other types of alopecia, FFA can affect patients' health-related quality of life (HRQOL). However, this effect has been rarely discussed. This study was designed to evaluate HRQOL in patients with FFA. METHODS: In this cross-sectional study, 49 patients with confirmed FFA were asked to complete Dermatology Life Quality Index (DLQI) and the 36-Item Short Form Survey (SF-36) questionnaires. Disease severity was evaluated with the Frontal Fibrosing Alopecia Severity Score Index (FFASI). RESULTS: Significant relation between SF-36 scores and other covariants was not detected. According to the DLQI, most of the patients (54%) had impaired HRQOL, which was of low grade for most of them (84%). Patients with face papules and patients who were in the group of nail, limb, and flexural involvement had significantly lower HRQOL (p-value 0.03). CONCLUSION: We found that FFA negatively impacts HRQOL, which was more pronounced in patients with involvement of other ostensible areas.

Association of coronary artery dominance and mortality rate and complications in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: Percutaneous coronary intervention (PCI) is the treatment of choice for patients with ST-segment elevation myocardial infarction (STEMI). Effect of coronary artery dominance on the patients' outcome following primary PCI (PPCI) is not fully investigated. We investigated the association of coronary artery dominance with complications and 1-year mortality rate of PPCI. MATERIALS AND METHODS: In this retrospective study, patients with STEMI treated with PPCI from March 2016 to February 2018 were divided into three groups based on their coronary dominancy: left dominance (LD), right dominance (RD), and codominant. Demographic characteristics, medical history, results of physical examination, electrocardiography, angiography, and echocardiography were compared between the groups. RESULTS: Of 491 patients included in this study, 34 patients (7%) were LD and 22 patients (4.5%) were codominant. Accordingly, 54 propensity-matched RD patients were included in the analysis. The demographics and comorbidities of the three groups were not different (P > 0.05); however, all patients in the RD group had thrombolysis in myocardial infarction (TIMI) 3, while five patients in the LD and five patients in the codominant group had a TIMI ≤2 (P = 0.006). At admission, the median left ventricular ejection fraction (LVEF) was highest in RD patients and lowest in LD and codominant patients (34%, P = 0.009). There was no difference in terms of success or complications of PCI, in-hospital, and 1-year mortality rate (P > 0.05). CONCLUSION: Patients with left coronary artery dominance had a higher value of indicators of worse outcomes, such as lower LVEF and TIMI ≤ 2, compared with RD patients, but not different rates of success or complications of PCI, in-hospital, and 1-year mortality. This finding may suggest that interventionists should prepare themselves with protective measures for no-reflow and slow-flow phenomenon and also mechanical circulatory support before performing PPCI in LD patients.