An intronic polymorphism of the gene Plakophilin-3 is associated with IVF failure

Background: Implantation failure is determined when transferred embryos fail to implant following in vitro fertilization (IVF). In recent years, many studies suggest that implantation failure could be related to several genetic factors. In the current study, authors aimed to investigate the association of PKP3 rs10902158 (G>A) polymorphisms with the risk of implantation failure after ICSI treatment.Methods: 97 women, who underwent ICSI treatment owing to male factor infertility, were prospectively recruited in this cross-sectional study. Genomic DNA was prepared from peripheral blood samples in order to analyze the polymorphism (rs10902158) at the PKP3 gene by PCR-RFLP. The Results were presented as a genotype (GG, GA, and AA), and their relationship to IVF outcome was analyzed.Results: The patients were divided into two groups according to clinical pregnancy: the pregnant group included 51 patients (53%) and the non-pregnant group included 46 patients (47%). The clinical pregnancy outcome was significantly different between genotypes, which was 0%, 45.8% and 58.8% in the patients having the genotype AA, GA and GG respectively (p-value = 0.03).Conclusions: The presence of the allele A of the PKP3 SNP rs10902158 is associated with a reduced clinical pregnancy outcome in the patients undergoing ICSI treatment and may be helpful predictor for implantation failure.

Plakophilin-2 gene mutation in Yunnan population with unexplained sudden death / 中华地方病学杂志

Objective To study the desmosomal protein plakophilin-2(PKP2)gene mutation of arrhythmogenic right ventricular cardiomyopathy (ARVC) in different populations of Yunnan unexplained sudden death (YUSD) areas,and explore the relationship between PKP2 gene mutation and YUSD.Methods Heart blood samples of YUSD cases (n =7) and venous blood samples of YUSD immediate family (n =30) and other family (n =11) members were collected.Basic situation and genetic relationship of YUSD immediate family and other family were investigated,and electrocardiography (ECG) was examined.DNA from blood samples was extracted and 15 exons of PKP2 gene were sequenced to analyze the mutation of PKP2 gene in different populations.Results A total of 10 people carried 11 PKP2 gene mutation sites with a mutation rate of 20.83％ (10/48).Two mutation sites were novel (p.G247R,p.T298N),and the new mutation sites were carried by two YUSD cases.Eight missense mutations were heterozygous mutations,two of the three synonymous mutations were heterozygous mutations,and one was homozygous synonymous mutation.The mutation sites were significantly concentrated in 4 exons,which were No.1 097 base of exon 4,No.819 and 893 bases of exon 3.2,No.739 base of exon 3.1,and No.156 base of exon 1.One YUSD case of ARVC pathological change carried exon 3.1 (p.G247R) and exon 4 (p.L366P) compound heterozygous mutations,the other YUSD case carried exon 3.2 (p.T298N) heterozygous mutation.The YUSD cases and immediate family with PKP2 gene mutations showed obvious family genetic relationships,and they were all first-degree and second-degree relatives.The abnormal ECGs of YUSD immediate family and other family mainly were conduction block,arrhythmia and premature beat.Conclusion There is a high PKP2 gene mutation rate in different populations of YUSD areas,and there may be a certain etiological connection between PKP2 gene mutations and YUSD.

Clinical profile in arrhythmogenic cardiomyopathy and a recessive plakophilin-2 gene mutation

Objective Arrhythmogenic cardiomyopathy (ACM) is not an uncommon cause of cardiac morbidity in Kashmir valley. This study was designed to document various clinical features and to sequence exons 11 and 12 of plakophilin 2 (PKP2) gene in these patients. Methods ACM patients who attended cardiology outpatient department of our institute from January 2014 to April 2015 were included in the study. Their records were reviewed. Controls were randomly selected, who had no history or family history of cardiac illness and had a normal cardiac examination. A blood sample was also taken from both the groups for sequencing of exon 11 and 12 of PKP2 gene. ACM patients were followed up until July 2016. Results Eleven ACM patients and seven controls were included in the study. Most common mode of presentation was ventricular tachycardia (VT). Two patients had left ventricular (LV) systolic dysfunction. One patient had a splice site mutation in exon 12 of PKP2 gene and one patient died during follow-up. One of the controls had an intronic variation that has no pathogenic significance vis-à-vis ACM. Conclusion Our study describes various clinical parameters in ACM patients and a recessive plakophilin 2 mutation after a limited PKP2 gene sequencing.

Ectodermal dysplasia-skin fragility syndrome.

Ectodermal dysplasia-skin fragility (EDSF) syndrome is a rare and first described inherited disorder of desmosomes. It occurs due to loss-of-function mutations in PKP1 gene resulting in poorly formed desmosomes and loss of desmosomal and epidermal integrity. We report a case of a 2-year-old Indian male child who presented with palmoplantar hyperkeratosis with fissuring, short, sparse, and easily pluckable scalp hair, nail dystrophy, and multiple erosions over the skin. Skin biopsy showed epidermal hyperplasia with widening of intercellular spaces. His developmental milestones were delayed but intelligence was normal. Echocardiography, X-ray chest, and electrocardiogram were normal. Very few cases of this syndrome have been reported in the literature. We consider this as the first case report from India.

Ectodermal Dysplasia/Skin Fragility Syndrome:The First Case Report in China / 中华皮肤科杂志

Objective To report the first case of ectodermal dysplasia/skin fragility syndrome in China. Methods The clinical data, transmission electron microscopic examination and immunohistochemical analysis of this patient were evaluated. Results The patient was a 3-year-old girl who presented increased skin fragility with trauma-induced, blisters and erosions, combined with short and sparse hair, finger-and toe-nail dystrophy and palmoplantar keratoderma. Transmission electron microscopy showed a loss of keratinocyte-keratinocyte adhesion, widening of intercellular spaces and a reduced number of hypoplastic desmosomes. Immunohistochemical analysis revealed a complete absence of staining for plakophilin 1. Conclusion Ectodermal dysplasia/skin fragility syndrome is a rare autosomal recessive inherited disease characterized by clinical manifestations as well as electron microscopic features and immunohistochemical evidence.