Nonsyndromic Early-Onset Epileptic Encephalopathies: Two Novel KCTD7 Pathogenic Variants and a Literature Review.

Early-onset epileptic encephalopathies (EOEE) affect cognitive, sensory, and motor development. Genetic variations are among the identifiable primary causes of these syndromes. However, some patients have been reported to be affected by EOEE without any other clinical symptoms and signs. We study the genotype and phenotype of patients with nonsyndromic early-onset epileptic encephalopathy (NSEOEE) and report 2 novel patients from Iran. A comprehensive search was conducted in PubMed, John Willy, Springer, Elsevier, and Google Scholar databases to collect related information of all the previously reported cases with KCTD7 mutations. Fifty-four patients (from 40 families) were investigated. Using trio-whole-exome sequencing (trio-WES) and Sanger sequencing, the possible genetic causes of the disorder were checked. The probable impacts of the identified variants on the KCTD7 protein structure and function were predicted. This study provided a detailed overview of all published KCTD7 mutations and 2 de novo ones. We identified 2 novel homozygous variants of uncertain significance, c.458 G > A p. Arg153His and c.529C > T (p.Arg177Cys), in KCTD7 (NM_153033.4) (Chr7(GRCh37)). There is a significant wide distribution of the KCTD7 gene causing NSEOEE among different populations. In conclusion, KCTD7 mutations demonstrate a diverse geographical distribution alongside a wide range of ethnicities. This highlights the importance of careful consideration in the WES data analysis. Mutations of this gene may be a common cause of NSEOEE. Also, this study imprints targeted therapeutic opportunities for potassium channelepsies such as KCTD7-related NSEOEE.

A novel missense variant in GPT2 causes non-syndromic autosomal recessive intellectual disability in a consanguineous Iranian family.

Intellectual disability (ID) affects 1-3% of the general population worldwide. Genetic factors play an undeniable role in the etiology of Non-Syndromic Intellectual disability (NS-ID). Nowadays, whole-exome sequencing (WES) technique is used frequently to identify the causative genes in such heterogeneous diseases. Herein, we subjected four patients with initial diagnostics of NS-ID in a consanguineous Iranian family. To find the possible genetic cause(s), Trio-WES was performed on the proband and his both healthy parents. Sanger sequencing was performed to confirm the identified variant by WES and also investigate whether it co-segregates with the patients' phenotype in the family. Using several online in-silico predictors, the probable impacts of the variant on structure and function of GPT2 protein were predicted. A novel variant, c.266A>G; p.(Glu89Gly), in exon 3 of GPT2 (NM_133443.3) was identified using Trio-WES. The candidate variant was also verified by Sanger sequencing. All affected members showed the common clinical features suffering from a non-progressive mild-to-severe ID. Also, different clinical observations compared to previously reported cases such as no facial features, no obvious structural malformations, ability to speak but with difficulty, and lack of any morphological defects were noted for the first time in this family. The c.266A>G; p.(Glu89Gly) variant reported here is the sixth variant identified up to now in the GPT2 gene, to be associated with NS-ID. Our data support the potential malfunction of the substituted GPT2 protein resulted from the novel variant, however, we strongly suggest confirming this finding more by doing functional analysis.

Aspects of psychosocial development in infertile versus fertile men.

BACKGROUND: Infertility is one of the most difficult life experiences that a couple might encounter. Infertility as a bio-psycho-social phenomenon, could influence all aspects of life. While paying special attention to the psychological aspects of infertility in couples; many studies have investigated the non-clinical aspects of infertility, however, they rarely have evaluated the psychosocial development of infertile versus fertile men. We aimed to study the effects of infertility on psychosocial development in men. METHODS: In fact, we designed the study based on "Erikson's theory of psychosocial development". We focused on the relationship between psychosocial development and some self-conceived indices. For this purpose, we divided the participants volunteers into two groups of cases (80 infertile men) and controls (40 fertile men) and asked them to complete a 112 (questions questionnaire based on "self description"). The statistical analysis was performed by SPSS (version 13) using independent t-test, Pearson correlation coefficient and analysis of covariance. A p-value <0.05 was considered significant. RESULTS: Data analysis showed significant inter and intra group differences. Infertile and fertile groups showed significant differences in trust, autonomy, generativity and integrity stages (p < 0.05). Infertile intergroup analysis represents us to higher scores in positive than negative stages. CONCLUSION: Infertility as a phenomenon had its own effects on the psychosocial development of infertile men. However, good coping skills are powerful tools to manage these myriad of feelings surrounding infertile men.

Relationship between sperm chromatin status and ICSI outcome in men with obstructive azoospermia and unexplained infertile normozoospermia.

This study was done to evaluate the effect of sperm source on chromatin integrity and ICSI outcomes. One hundred and thirteen samples containing epididymal aspirates of 57 obstructive azoospermic men and 56-ejaculated semen of normozoospermic men were included in this study. Sperm chromatin status was evaluated by Chromomycin A3 (CMA3), Aniline Blue (AB) and Toluidine Blue (TB). Fertilization rate and embryo quality were recorded. In epididymal group the percentage of sperms stained with AB, CMA3 and TB were significantly higher compared to ejaculate group while fertilization rate (60.6% vs. 74.04%) was significantly lower. However, embryo quality was not significantly different between two groups. In addition, abnormal sperm chromatin condensation and DNA fragmentation were not correlated with fertilization rate and embryo quality. Our results highlight the role of epididymis in sperm maturation and confirm that ICSI using ejaculated sperm is the gold standard for treatment of infertile men.

Study of body image in fertile and infertile men.

BACKGROUND: Body Image as a multidimensional entity is related to both physical and psychological aspects of the image one has of his or her own body. Lack/absence of an acceptable body image is one of the reasons of mental distress in infertile individuals. METHODS: In this study, an equal number (No=120) of fertile and infertile men attending Avicenna Infertility Clinic (AIC) were enrolled. The participants were compared in regard to body image variables based on the "Multidimensional Body-Self Relations Questionnaire (MBSRQ)" consisting of 10 subscales. Data was analyzed by SPSS, version 11.5, using Chi square and independent t-tests. RESULTS: Fertile men had a more positive body image as compared to infertile individuals. Significant statistical differences were observed when body image subscales were compared in both groups; in other words appearance evaluation, appearance orientation, Novy, health evaluation, health orientation, illness orientation, body satisfaction, overweight preoccupation and self-classified weight showed differences, while no significant difference was observed in regard to fitness orientation. CONCLUSION: It seems that the ability and efficiency of body image is affected by infertility leading to dissatisfaction of one's body image.