Delineation of phenotypes and genotypes related to cohesin structural protein RAD21

RAD21 encodes a key component of the cohesin complex, and variants in RAD21 have been associated with Cornelia de Lange Syndrome (CdLS). Limited information on phenotypes attributable to RAD21 variants and genotype–phenotype relationships is currently published. We gathered a series of 49 individuals from 33 families with RAD21 alterations [24 different intragenic sequence variants (2 recurrent), 7 unique microdeletions], including 24 hitherto unpublished cases. We evaluated consequences of 12 intragenic variants by protein modelling and molecular dynamic studies. Full clinical information was available for 29 individuals. Their phenotype is an attenuated CdLS phenotype compared to that caused by variants in NIPBL or SMC1A for facial morphology, limb anomalies, and especially for cognition and behavior. In the 20 individuals with limited clinical information, additional phenotypes include Mungan syndrome (in patients with biallelic variants) and holoprosencephaly, with or without CdLS characteristics. We describe several additional cases with phenotypes including sclerocornea, in which involvement of the RAD21 variant is uncertain. Variants were frequently familial, and genotype–phenotype analyses demonstrated striking interfamilial and intrafamilial variability. Careful phenotyping is essential in interpreting consequences of RAD21 variants, and protein modeling and dynamics can be helpful in determining pathogenicity. The current study should be helpful when counseling families with a RAD21 variation.Spanish Ministry of Science, Innovation and Universities/State Research Agency RTC-2017-6494-1 and RTI2018-094434-B-I00 (MCIU/AEI/FEDER, UE) as well as funds from the European JPIAMR-VRI network “CONNECT” to PG-

Phylogeny and systematics of Anatolian mountain frogs

Kalayci, Gokhan/0000-0003-1255-496XWOS: 000408072700006Anatolian mountain frogs (Rana macrocnemis, Rana camerani, Rana holtzi, and Rana tavasensis) are one of the most specious amphibian groups in Turkey containing two endemic taxa (R. holtzi and R. tavasensis). the taxonomy of this group remains controversial as there are several unresolved issues. in the present study, we aimed to resolve the taxonomic uncertainty of the Anatolian mountain frogs through two mitochondrial genes (CYTB, 481 bp and COI, 743 bp) and two protein-coding nuclear genes (POMC, 401 bp and RAG1, 717 bp). the mitochondrial DNA (mtDNA) markers were found to be highly polymorphic in this group. Haplotype network analysis revealed that R. tavasensis was different for at least 33 and 52 mutational steps according to CYTB and COI gene regions, respectively. High bootstrap and posterior probability values obtained from the mtDNA genes support the idea that Anatolian mountain frogs are represented by two distinct species in Anatolia: R. macrocnemis and R. tavasensis. However, no genetic variation was detected according to nuclear DNA (nDNA) markers. the analysis of molecular variance (AMOVA) revealed no differences among the groups of R. macrocnemis, R. camerani, and R. holtzi. Despite the low genetic distance among R. macrocnemis, R. camerani, and R. holtzi species, the pairwise distances estimated from R. tavasensis were higher compared with other Anatolian mountain frog lineages. (C) 2017 Elsevier Ltd. All rights reserved.Recep Tayyip Erdogan University (Rize, Turkey)Recep Tayyip Erdogan University [Bap-2013.102.03.10, 2015.53001.102.03.05]This research was funded by Grant Bap-2013.102.03.10 and 2015.53001.102.03.05 of the Recep Tayyip Erdogan University (Rize, Turkey). We are thankful to Bilal Kutrup and Yusuf Bekta for their contribution during this research. Also, we thank to Kurtulu Olgun who provided tissue samples from Izmir and Denizli localities

Association between insulin resistance and serum and salivary irisin levels in patients with psoriasis vulgaris

Background/Objectives: Psoriasis is an inflammatory skin disease, which is associated with metabolic syndrome and insulin resistance. Irisin is an adipokine and myokine that regulates the metabolic status during times of increased insulin sensitivity. In this study, we aimed to investigate changes in the serum level of irisin in psoriasis patients in comparison with participants who did not have any disease (control group). We hope the results of our study would also aid in establishing a protocol aimed at understanding the etiopathogenesis and treatment of psoriasis. Materials and methods: The study included 30 patients with psoriasis vulgaris, who presented to the dermatology outpatient clinic and were not receiving systemic treatment. The control group included voluntary participants who did not have any disease (n = 30). In addition to venous and salivary irisin levels, glucose, triglyceride, cholesterol, high-density lipoprotein, and low-density lipoprotein levels, and Homeostasis Model Assessment of Insulin Resistance scores were measured in both control and patient groups. Results: Serum irisin and salivary irisin levels were significantly lower in the patient group compared with the control group (p < 0.05). In the patient group, serum irisin levels had a positive correlation with salivary irisin levels (r = 418; p = 0.022) and a negative correlation with Psoriasis Area and Severity Index (r = −437, p = 0.016) and Dermatological Life Quality Index (r = −424; p = 0.02) scores. Conclusion: This is the first study evaluating irisin levels in patients with psoriasis vulgaris in the literature. The results of our study show that serum and salivary irisin levels were significantly lower in the patient group when compared with the control group. Irisin levels in patients with severe psoriasis were low, suggesting that irisin may have a role in the pathogenesis of psoriasis and may be a marker showing the severity of psoriasis, which could warn us against the development of insulin resistance and diabetes mellitus

On the age structure of two samples of Lacerta trilineata BEDRIAGA, 1886, from different altitudes in Turkey (Squamata: Sarnia: Lacertidae)

WOS: 000443667400001The authors studied the age composition in two samples (Edirne: 17 m a.s.l. and Bolu: 1,250 m a.s.l.) of Lacerta trilineata BEDRIAGA, 1886, in Turkey. Aging by skeletochronology showed that the maximum age of the lizards was about seven years in the Bolu and five in the Edirne sample. the adult survival rate was 0.59 % in males and 0.24 % in females of Bolu. the adult life expectancy was calculated as 2.94 years for males and 1.82 for females in the Bolu sample. Age at sexual maturity was two years in both samples. Although the mean age of the high altitude sample was older than of the low altitude sample, the mean snout-vent-length of the latter was longer

Clinical Characteristics and Mutation Spectrum of Neurofibromatosis Type 1 in 27 Turkish Families

Background: Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder that results in a predisposition to the growth of multiple tumors in the central nervous system, the peripheral nervous system, and the skin. The clinical manifestations of neurofibromatosis are associated with loss of neurofibromin expression which causes the upregulation of the RAS pathway. Although neurofibromatosis type 1 can be diagnosed based on the National Institutes of Health criteria, sometimes the diagnosis is difficult, in cases where the characteristic features do not develop. Moreover, other RAS-related disorders may present with significantly overlapping clinical features

Age Structure and Body Size Variation in Common Toad (Bufo bufo, Linnaeus 1758) from Three Different Altitudes in Turkey

gul, serkan/0000-0002-0372-7462WOS: 000478004100011We describe here for the first time the body size and age of the Common Toad (Bufo bufo) from high (Trabzon, 1090 m and Kastamonu, 925 m above sea level) and low (Yalova, 65 m above sea level) altitudes in Turkey using skeletochronology. the specimens from Trabzon were significantly smaller and younger than the ones from the Kastamonu and Yalova populations. Age at sexual maturity was three years for females while it varied between two to three years in males in all three populations. We found the females to be significantly larger than males in all three populations. the sexual dimorphism indices (SDI) were biased toward the female populations. Even after accounting for the influence of age, the snout-vent length (SVL) differed significantly among the populations. Age and SVL were closely correlated in the male populations for all the three localities (Yalova, Kastamonu, and Trabzon) and for female individuals in the Trabzon population. in this first report, we reveal the demographic structure of B. bufo from the Anatolia region in Turkey and provide comparative data regarding this species for further discussion and determined that age and body size of Common Toad not differentiated among different altitudes

Clinical, Cytogenetic and Molecular Cytogenetic Outcomes of Cell-Free DNA Testing for Rare Chromosomal Anomalies

The scope of cell-free DNA (cfDNA) testing was expanded to the genome, which allowed screening for rare chromosome anomalies (RCAs). Since the efficiency of the test for RCAs remains below the common aneuploidies, there is a debate on the usage of expanded tests. This study focuses on the confirmatory and follow-up data of cases with positive cfDNA testing for RCAs and cases with screen-negative results in a series of 912 consecutive cases that underwent invasive testing following cfDNA testing. Chorion villus sampling (CVS), amniocentesis (AS), fetal blood sampling, and term placenta samples were investigated using classical cytogenetic and molecular cytogenetic techniques. Out of 593 screen-positive results, 504 (85%) were for common aneuploidies, 40 (6.7%) for rare autosomal trisomies (RATs), and 49 (8.3%) for structural chromosome anomalies (SAs). Of the screen-positives for RATs, 20 cases were evaluated only in fetal tissue, and confined placental mosaicism (CPM) could not be excluded. Among cases with definitive results (n = 20), the rates of true positives, placental mosaics, and false positives were 35%, 45%, and 10%, respectively. Among screen-positives for SAs, 32.7% were true positives. The confirmation rate was higher for duplications than deletions (58.3% vs. 29.4%). The rate of chromosomal abnormality was 10.9% in the group of 256 screen-negatives with pathological ultrasound findings. This study provides further data to assess the efficiency of expanded cfDNA testing for RATs and SAs. The test efficiency for cfDNA seems to be higher for duplications than for deletions, which is evidence of the role of expert ultrasound in identifying pregnancies at increased risk for chromosome anomalies, even in pregnancies with screen-negatives. Furthermore, we discussed the efficiency of CVS vs. AC in screen-positives for RATs

Functional loss of ubiquitin-specific protease 14 may lead to a novel distal arthrogryposis phenotype

Multiple congenital contractures (MCC) comprise a number of rare, non-progressive conditions displaying marked phenotypic and etiologic heterogeneity. A genetic cause can be established in approximately half of the affected individuals, attributed to genetic defects in the formation and functioning of the central and peripheral nervous system, neuromuscular junctions, skeletal muscles, and connective tissue. Ubiquitin-specific protease 14 (USP14) encodes a major proteasome-associated deubiquitinating enzyme with an established dual role as an inhibitor and an activator of proteolysis, maintaining protein homeostasis. Usp14-deficient mice show a phenotype similar to lethal human MCC phenotypes, with callosal anomalies, muscle wasting, and early lethality, attributed to neuromuscular junction defects due to decreased monomeric ubiquitin pool. We describe a new, autosomal recessive MCC phenotype in three fetuses from two different branches of a consanguineous family, presenting with distal arthrogryposis, underdevelopment of the corpus callosum, and dysmorphic facial features. Exome sequencing identified a biallelic 4-bp deletion (c.233_236delTTCC; p.Leu78Glnfs*11, SCV002028347) in USP14, and sequencing of family members showed segregation with the phenotype. RT-qPCR experiment in an unaffected heterozygote revealed that mutant USP14 was expressed, indicating that abnormal transcript escapes nonsense-mediated mRNA decay. We propose that herein described fetuses represent the first human phenotype of USP14 loss, with callosal anomalies and/or cortical malformations, multiple contractures, and recognizable dysmorphic facial features