Underexpression of hsa-miR-449 family and their promoter hypermethylation in infertile men: A case-control study

Background: Post-transcriptional microRNAs (miRNAs) have an important pattern in the spermatogenesis process. Objective: Study of the expression and methylation of hsa-miR-449 family in sperm samples of infertile men. Materials and Methods: In this case-control study, we recruited 74 infertile men (with asthenozoospermia, teratozoospermia, asthenoteratozoospermia, and oligoasthenoteratozoospermia) and 30 control samples. Methylation-specific PCR (MSP) method was used for methylation evaluation of hsa-miR-449 a, b, c promoter. By Real time PCR (qRT-PCR) method,we showed downregulation of hsa-miR-449 a, b, c in the sperm samples of infertile men and compared it to their fertile counterparts. Results: There was significant underexperssion, in hsa-miR-449-b in oligoasthenoteratospermic samples (p = 0.0001, F = 2.9). About the methylation pattern, infertile men showed high frequency of methylation in the promoter of hsa-miR-449 a, b, c in comparison to controls (60.8% vs 23.3%), the highest amount of methylation was observed in oligoasthenoteratospermia samples (81.2%). Conclusion: In this study, low expression and high methylation of hsa-miR-449-b were observed in infertile men in compared to control samples, which can be one of the causes of defective spermatogenesis. Key words: Spermatogenesis, miR-449, Expression, Epigenetic

Identification of two novel homozygous nonsense mutations in TRAPPC9 in two unrelated consanguineous families with intellectual Disability from Iran

Background: Pathogenic mutations in TRAPPC9 are associated with autosomal recessive Intellectual Disability (ID), a major public health issue that affects about 1–3% of children worldwide. Method: Clinical evaluation, magnetic resonance imaging, peripheral blood karyotype, Multiplex ligation-dependent probe amplification (MLPA), array CGH, and whole-exome sequencing were used to characterize etiology in three patients from two unrelated consanguineous families of Iranian descent with intellectual disability. Results: Whole-exome sequencing showed two novel homozygous nonsense mutations (c.937C>T) in exon 3 and (c.3103C>T) in exon 19 of TRAPPC9 (NM_031466.7) in two unrelated consanguineous families. Conclusion: The two novel variants found in TRAPPC9 caused truncated protein and clinical manifestations such as ID, developmental delay, microcephaly, and brain abnormalities in three patient