Simultaneous Identification of Both MFSD8 and RDH12 Pathogenic Variants in a Chinese Family Affected With Retinitis Pigmentosa

Retinitis pigmentosa (RP) is characterized by tremendous genetic and phenotypic heterogeneity. Here, we investigate the pathogeny of RP in a family to provide evidence for genetic and reproductive counseling for families. Although this pregnant woman of 8+3 weeks presented with RP, her first baby was born with RP, epilepsy, and cerebellar atrophy. The research identified a compound heterozygous mutation (c.998+3_998+6del/deletion) in the MFSD8 gene of the first born, explaining the cause of the proband’s disease, which cannot explain the mother’s. Then, a homozygous mutation c.343+1G > A in RDH12 of the mother was found. RT-PCR is employed to find that there is a skipping of exon 10 in MFSD8 and a 15-nucleotide retention of intron5 in RDH12. The coexistence of two independent instances of RP caused by distinct genes in one pedigree is demonstrated. Based on the diagnosis, a prenatal diagnosis performed on the fetus found that the fetus’s MFSD8 is affected by the same mutation as the proband. The research underscoring the complexity of RP and the need for the combination of extensive molecular genetic testing and clinical characterization in addition expands the spectrum of MFSD8 mutations. Finally, it is expected that the family members would be prevented from reproducing children with the similar disease.

Novel Mutations in X-Linked, USP26-Induced Asthenoteratozoospermia and Male Infertility

Male infertility is a multifactorial disease with a strong genetic background. Abnormal sperm morphologies have been found to be closely related to male infertility. Here, we conducted whole-exome sequencing in a cohort of 150 Han Chinese men with asthenoteratozoospermia. Two novel hemizygous mutations were identified in USP26, an X-linked gene preferentially expressed in the testis and encoding a deubiquitinating enzyme. These USP26 variants are extremely rare in human population genome databases and have been predicted to be deleterious by multiple bioinformatics tools. Hematoxylin-eosin staining and electron microscopy analyses of the spermatozoa from men harboring hemizygous USP26 variants showed a highly aberrant morphology and ultrastructure of the sperm heads and flagella. Real-time quantitative PCR and immunoblotting assays revealed obviously reduced levels of USP26 mRNA and protein in the spermatozoa from men harboring hemizygous deleterious variants of USP26. Furthermore, intracytoplasmic sperm injections performed on infertile men harboring hemizygous USP26 variants achieved satisfactory outcomes. Overall, our study demonstrates that USP26 is essential for normal sperm morphogenesis, and hemizygous USP26 mutations can induce X-linked asthenoteratozoospermia. These findings will provide effective guidance for the genetic and reproductive counseling of infertile men with asthenoteratozoospermia.

Post-Transplant Pregnancy and Contraception

Placed in a historic context, this overview focuses on post-transpant pregnancy, fatherhood, and contraception in women and men. The critical importance of early reproductive counseling because of improved sexual function and the early return of ovulation and menses post-transplant is emphasized. We explain the decision making regarding contraception choices. The available data on the safety of immunosuppressive drugs in pregnancy, and for men desiring fatherhood, are detailed. The risk of maternal ingestion of mycophenolate products on the in utero fetus is considered and contrasted with the lack of concern for their use by men fathering children. Pregnancy risks to the allograft, baby, and mother are discussed. An infant’s exposure to specific immunosuppressant medications through breastfeeding is reviewed. The ethics and realities of post-transplant parenthood are explored.

Chromosomal Abnormalities in Couples with Primary and Secondary Infertility: Genetic Counseling for Assisted Reproductive Techniques (ART)

Background: World Health Organization estimates that 60-80 million couple world-wide currently suffer from infertility. Recurrent pregnancy loss (RPL) is also another major concern. Chromosomal rearrangements play a crucial role in primary and secondary infertility and RPL. Underlying genetic abnormalities like chromosomal abnormalities contribute to 5-10% of the reproductive failures. The aim of the study was to evaluate the chromosomal abnormalities in infertility and RPL cases to help obstetrician/fertility experts to carry out risk assessment and provide appropriate assisted reproductive techniques for better management of the problem. Methods: Karyotyping was performed for 414 cases with the history of infertility and RPL over a period of one year. Samples were processed according to procedures of AGT cytogenetic laboratory manual. Results: Chromosomal abnormalities were observed in 15% of cases. Robertsonian translocation, reciprocal translocation, inversion, derivatives, marker chromosomes, mosaics, aneuploidy and polymorphic variants each contributed 2%, 3%, 3%, 13%, 2%, 10%, 6% and 61%, respectively. Conclusion: Evaluation of chromosomal abnormalities in couple is warranted prior to planning pregnancy especially for assisted reproductive management cases. Chro-mosomal analysis can be used as one of the diagnostic tools by OBG/IVF specialists in association with geneticist/genetic counselor for proper reproductive counseling and management.

Faktor Personal yang Mempengaruhi Perilaku Seksual Pranikah Beresiko Infeksi Menular Seksual (IMS ) : Teori Sosial Learning di Siswa SMA Malang

Berdasarkan data Tim Survei dari Sebaya dan FK Unair pada tahun 2005 di kota Surabaya dari 126 responden yang berusia 19-23 tahun mendapat hasil bahwa 13,5% responden mengaku pernah melakukan hubungan seks pranikah. Tujuan penelitian melihat faktor personal yang mempengaruhi perilaku seksual pranikah beresiko IMS. Penelitian menggunakan teori perilaku Bandura. Penelitian ini explanatory research dengan desain penelitian cross sectional. Sampel penelitian ini dilakukan simple random sampling sebanyak 318 responden. Hasil analisa chi square p= 0,05 didapatkan memiliki pengaruhi signifikan pada responden laki-laki yaitu tingkat religiusitas (p=0,012) sedangkan pada wanita (p=0,562) dan tingkat religiusitas kurang tekun memiliki kecenderungan 2,4 kali lebih besar melakukan perilaku seksual beresiko IMS, efikasi diri (p=0,004) memiliki efikasi diri rendah memiliki kecenderunan 2,1 kali lebih besar untuk perilaku seksual beresiko IMS sedangkan 1 variabel yang berhubungan pada responden perempuan dengan perilaku seksual pranikah yang beresiko terhadap IMS yaitu efikasi diri (p=0,001). Untuk pengetahuan baik terhadap pada responden laki-laki (p=0,153) maupun perempuan (p= 0,668),tidak ada hubungan yang signifikan. Untuk sikap responden bahwa pada responden laki-laki (p=0,162) dan perempuan (p=1,000) tidak terdapat hubungan yang signifikan. Untuk Gender bahwa baik pada responden laki-laki (p=1,000) maupun perempuan (p=0,340) tidak ada hubungan yang signifikan. Tingkat religiusitas OR=2,378 artinya responden yang memiliki tingkat religiusitas kurang tekun memiliki kecenderunan 2,4 kali lebih besar untuk melakukan perilaku seksual beresiko IMS dibandingkan responden tingkat religiusitas tinggi. Efikasi OR=2,090 artinya responden yang efikasi diri rendah memiliki kecenderunan 2,1 kali lebih besar untuk perilaku seksual beresiko IMS. Saran untuk mengaktifkan program Pusat Informasi dan Konseling-Kesehatan Reproduksi Remaja (PIK-KRR). Based on data from the survey teams from Peer and FK Unair in 2005 in the city of Surabaya126 respondents aged 19-23 years found that 13.5% of respondents claimed to have had premarital sex The purpose is to look at personal factors that influence premarital sexual behavior at risk for STIs.. Sampling this study by simple random sampling. The results chi square with p=0.05 that have a significant namely the level of religiosity (p = 0.012) and respondents who have less religiosity have a 2.4 times greater to engage more likely to engage in sexual behavior at risk for STIs while there is variable related to female respondents with premarital sexual behavior that is at risk for STIs efficacy self (p = 0.001). For knowledge of both male (p = 0.153) and female respondents (p = 0.668), there is no relationship. For the attitude of respondents that the male respondents (p = 0.162) and women (p = 1,000) .For Gender that both male respondents (p = 1,000) andwomen (p = 0.340). From the result religiosity OR = 2.337 means that respondents who have a less persistent level of religiosity have a tendency of 2.4 times compared with respondents with a high degree of religiosity. And the efficacy of having OR = 2,090 means that respondents who have low self-efficacy have a tendency of 2.1 times more to do sexual behavior at risk of STIs. Suggestions to activate the Information and Adolescent Reproductive Counseling-Health (PIK-KRR) program for high schools.

Müllerian Duct Anomalies- Diagnostic Imaging in Pediatric and Adolescent Population

Müllerian duct anomalies (MDAs) are congenital entities that result from the non-development, defective vertical or lateral fusion, or the resorption failure of the Müllerian (paramesonephric) ducts. MDAs represent a more frequent entity than previously believed. Few recent meta-analyses reported a prevalence of 5.5 - 6.7%. MDAs are commonly associated with other anomalies, specially kidneys, so identification of both kidneys is important. In pediatric and adolescent population MDAs are discovered incidentally at patients observed for some other reason or because of the primary amenorrhea and low abdominal pain related to hematometra (colpos). Imaging is essential for a diagnosis, management, and reproductive counseling in patients with MDA. Patients suspected of having the MDA are often initially referred to pelvic ultrasonography (US). Field-of-view restrictions with US, patient body habitus and artifact from bowel gas may result in a request for the further MagneticRresonance Iimaging (MRI). Also US cannot help identify the type of the MDA. MRI is the imaging standard of reference because it is non-invasive, does not involve ionizing radiation, has a multiplanar capability, allows an excellent soft-tissue characterization, detailed delineation of the uterovaginal anatomy and accurate classification of the type of anomaly. This is especially true for young female patients, in whom the use of vaginal US probes is avoided. Establishing an accurate diagnosis is essential for planning treatment and management strategies. The surgical management of MDAs is specific to the type of malformation and may vary in a specific group.

Identification of DNAH6 mutations in infertile men with multiple morphological abnormalities of the sperm flagella

Male infertility due to spermatogenesis defects affects millions of men worldwide. However, the genetic etiology of the vast majority remains unclear. Here we describe three men with primary infertility due to multiple morphological abnormalities of the sperm flagella (MMAF) from two unrelated Han Chinese families. We performed whole-exome sequencing (WES) and Sanger sequencing on the proband of family 1, and found that he carried novel compound heterozygous missense mutations in dynein axonemal heavy chain 6 (DNAH6) that resulted in the substitution of a conserved amino acid residue and co-segregated with the MMAF phenotype in this family. Papanicolaou staining and transmission electron microscopy analysis revealed morphological and ultrastructural abnormalities in the sperm flagella in carriers of these genetic variants. Immunostaining experiments showed that DNAH6 was localized in the sperm tail. This is the first report identifying novel recessive mutations in DNAH6 as a cause of MMAF. These findings expand the spectrum of known MMAF mutations and phenotypes and provide information that can be useful for genetic and reproductive counseling of MMAF patients.