Pelizaeus-Merzbacher-Like Disease 1 Caused by a Novel Mutation in GJC2 Gene: A Case Report.

Pelizaeus-Merzbacher-Like Disease 1 is a genetic disorder affecting the central nervous system with an autosomal recessive inheritance pattern. It is a rare genetic disorder that affects the central nervous system. In this report, we demonstrated the clinical and paraclinical features of an Iranian consanguine pedigree with suspected hypomyelinating leukodystrophy, without any defined diagnosis. The proband, a 15-month-old girl, visited the Razi pathobiology and medical genetic laboratory of Karaj, where the study was conducted in 2020. Following whole-exome sequencing analysis of the proband and segregation analysis, a novel pathogenic mutation was discovered. GJC2 (NM_020435.4):c.1096dupG was found to be homozygous in the proband and heterozygous in both parents. This mutation was in the coding region of the protein, which results in D366Gfs*126 (p.Asp366GlyfsTer126). The site of mutation was at the 3' region of the connexin superfamily domain. The frameshift results in a different peptide sequence of the C-terminal and extended protein. Our findings led to the diagnosis of the proband's disease as Pelizaeus-Merzbacher-Like Disease 1 and led to the end of the diagnostic odyssey. We provided effective genetic counseling through the identification of a novel pathogenic mutation in gap junction protein C2 in this family and suggested preimplantation genetic diagnosis for the next pregnancy. Furthermore, our findings confirmed the association of GJC2 mutations with PMLD1. This discovery added to the repertoire of genetic mutations of Pelizaeus-Merzbacher-Like Disease 1. This knowledge could be applied for expanded carrier screening of other families, especially for Iranian consanguine marriages.

Coding and Non-Coding RNAs, as Male Fertility and Infertility Biomarkers.

Semen analysis is usually the first step in the assessment of male fertility. Although analyzes provide valuable information about male fertility, success of cytoplasmic sperm injection using this method is not predictable. In the recent years, studies have shown that sperm quality assessment helps clinicians predict male fertility status based on the expression of biomarkers. To write this article, a comprehensive study was conducted on several RNA transcripts by searching related words on medical information databases by 2018. According to the literature, spermatogenesis based disorders in male infertility have a significant relationship with the expression level of some RNA molecules (like DAZ and PRM1/PRM2 ratio) in semen and testicular tissue. Thus, they might be used as predictor biomarkersto evaluate success rate of testicular sperm extraction (TESE) procedure, but confirmation of this hypothesis requires more extensive research. By comparing the number of RNAs attributed to each fertility disorder in men, it is possible to trace the causes of disease or return fertility to some infertile patients by regulating the mentioned molecules. Further researches can provide a better understanding of the use of RNA expression profiles in the diagnosis and treatment of male infertility.