Genetic study of sex inversion in humans

Sex reversal is considered to be a form of disorders of sex development or DSD (disorders/Differences of sex development). This is an inconsistency between gonadal, phenotypic and chromosomal sex. Sexual development, including the development of gonads and organs reproduction and the acquisition of secondary sexual characteristics, is under genetic control. Indeed, following the bibliographic study carried out in this report, we were able to better understand the pathophysiology of sex reversal, enumerate the associated genetic mutations and identify the signaling pathways affected. In addition, a retrospective study was performed to determine the frequency of sex reversal compared to other categories of DSD. This work focused on a sample of 981 patients with clinical signs indicating the presence of DSD. These patients presented to the Cytogenetics laboratory of the Institut Pasteur in Morocco between the years 2011 and 2021. The karyotype was performed on a heparinized tube according to the standard method. Based on the karyotype results, we found 74 cases of sex inversion corresponding to 7.54%. Abnormal karyotypes accounted for 37.31% with a predominance of Turner syndrome (41.53%), 26.23% of Klinefelter syndrome, 12.3% of patients presented with XY female type sex inversion, 7.92% with sex reversal type XX men and 7.65% had mixed gonadal dysgenesis. Finally, to guide the diagnosis, we established a course of action indicating the genes which are the most incriminated in the two types of sex inversion

Prader-Willi syndrome: Methylation study or fluorescence in situ hybridization first?

Prader-Willi syndrome (PWS) is neurogenetic disorder involving the imprinting mechanism at 15q11-13 region. We report a 4-year-old girl who was referred to our laboratory to be investigated for clinical obesity, mental deficiency and respiratory problems. The patient was born for non-consanguineous and healthy biological parents. After normal pregnancy, the patient was delivered by cesarean section at full term, with a birth weight of 2500 g, and the height and head circumference were unknown. In neonatal stage, she presented severe hypotonia with feeding problems. Her developmental progress was delayed. She walked and developed speech at the age of 3 years. Since the age of 3 years, she presented severe dental problems. Methylation study had confirmed the diagnosis, and for detecting etiology, fluorescence in situ hybridization using probes for small nuclear ribonucleoprotein polypeptide N (SNRPN), which map inside the chromosomal region 15q11-15q13, was necessary to confirm the 15q11-15q13 deletion of paternal chromosome 15, which is the predominant genetic defect in PWS. In conclusion, we report this case with an objective to reinforce the necessity of analysis of DNA methylation within the 15q11-13 region, which is an important tool for the correct diagnosis among children presenting with neonatal hypotonia, mental deficiency and obesity

Prader-Willi syndrome: Methylation study or fluorescence in situ hybridization first?

Prader–Willi syndrome (PWS) is neurogenetic disorder involving the imprinting mechanism at 15q11–13 region. We report a 4-year-old girl who was referred to our laboratory to be investigated for clinical obesity, mental deficiency and respiratory problems. The patient was born for non-consanguineous and healthy biological parents. After normal pregnancy, the patient was delivered by cesarean section at full term, with a birth weight of 2500 g, and the height and head circumference were unknown. In neonatal stage, she presented severe hypotonia with feeding problems. Her developmental progress was delayed. She walked and developed speech at the age of 3 years. Since the age of 3 years, she presented severe dental problems. Methylation study had confirmed the diagnosis, and for detecting etiology, fluorescence in situ hybridization using probes for small nuclear ribonucleoprotein polypeptide N (SNRPN), which map inside the chromosomal region 15q11–15q13, was necessary to confirm the 15q11–15q13 deletion of paternal chromosome 15, which is the predominant genetic defect in PWS. In conclusion, we report this case with an objective to reinforce the necessity of analysis of DNA methylation within the 15q11–13 region, which is an important tool for the correct diagnosis among children presenting with neonatal hypotonia, mental deficiency and obesity

The polymorphism G894 T of endothelial nitric oxide synthase (eNOS) gene is associated with susceptibility to essential hypertension (EH) in Morocco

Abstract Background Hypertension is a multifactorial disease involving both environmental and genetic Factros. G894 T eNOS polymorphism has been suggested to be responsible for reduced NO synthesis, and EH development. The objective of our case-control study is to evaluate the potential association of G894 T eNOS polymorphism with Essential Hypertension (EH) susceptibility, among a sample of Moroccan patients. Methods One hundred forty five hypertensive patients were recruited from the department of Cardiology, University Hospital Center Ibn Rochd, Casablanca, Morocco, and compared to 184 apparently healthy subjects. DNA samples were genotype by PCR-RFLP method using MboI restriction enzyme. Results Our results showed a positive correlation between G894 T eNOS distribution and Alcohol and Obesity rik factors (P = 0.009 and 0.02 respectively). Patients with elevated Cardio Vascular Risk (CVR) carried out the higher frequency of homozygous mutant genotype TT (62.2%) and T mutant allele (77.8%), compared to median and low CVR groups. G894 T eNOS distribution was significantly associated to a high risk of EH occurrence under the GT and TT genotypes (OR [95% CI] = 20.2 [7.7–52.4], P <  0.0001; OR [95% CI] = 332.5 [98.2–1125.4], P <  0.0001 respectively), and the 3 genotypic transmission models (Dominant: OR [95% CI] = 43.2 [17.9–104.09], P <  0.0001; Recessive: OR [95% CI] = 47.7 [18.6–122.3]; P <  0.0001; Additive: OR [95% CI] = 14.02 [9.6–20.45], P <  0.0001). Conclusion Our study suggests a strong association of G894 T eNOS polymorphism with susceptibility to EH in Morocco. Studies trying to identify contributing genes may be very useful and allow recognizing the vulnerable individuals and classifying patients in subgroups with definite genetic and pathogenic mechanisms to achieve better prevention and therapeutics

Chromosome Abnormalities Related to Reproductive and Sexual Development Disorders: A 5-Year Retrospective Study

Chromosomal abnormalities are the main genetic risk factor associated with reproductive and sexual development disorders (DSD). The goal of this study is to retrospectively evaluate the frequency of chromosomal aberrations in Moroccan subjects with problems of procreation or sexual ambiguity. A total of 1005 individuals, including 170 infertile couples, underwent cytogenetic analysis in the Cytogenetic Laboratory of the Pasteur Institute of Morocco. Heparinized blood samples were processed according to the standard karyotype method. A total (81.5%) of the patients studied had a normal karyotype, while the remaining (18.5%) patients had an abnormal karyotype. Female patients had more chromosomal abnormalities (52%) than male patients (48%). These chromosomal aberrations included 154 cases (83%) of sex chromosomal abnormalities, the most common being Turner’s syndrome and Klinefelter’s syndrome, and 31 cases (17%) had autosomal aberrations, especially chromosome 9 reversal (inv(9)(p12;q13)). The present data shows that among 170 couples, 10.6% had chromosomal abnormalities mainly involved in the occurrence of recurrent miscarriages. Genotype-phenotype correlations could not be made, and therefore, studies using more resolutive molecular biology techniques would be desirable

Analysis of the influence of glutathione S-transferase (GSTM1 and GSTT1) genes on the risk of essential hypertension

Background Essential hypertension (EH) results from a complex interaction between environmental factors and an individual’s genetic background. Aim To assess the relationship between polymorphisms in GSTM1 and GSTT1 and the risk of EH. Subjects and methods A multiplex-PCR was used to identify the genotypic profiles of GSTM1 and GSTT1 in 160 patients and 210 controls. Results The frequency of GSTM1-null genotype was higher in patients younger than 61 years when compared to those over 61 years. Interestingly, GSTT1-null was significantly associated with the risk of EH (OR 4; 95% CI 2.6–6.3; p < 0.0001). While GSTM1-null showed no trend (OR 0.7; 95% CI 0.5–1.1, p = 0.12). Individuals carrying the combined GSTT1-null/GSTM1-null were 2.4 times more at risk for hypertension compared to those harbouring the combined GSTT1-present/GSTM1-present genotype (OR 2.4; 95% CI 1.3–4.4; p = 0.005). Additionally, the presence of the combined GSTT1-null/GSTM1-present was associated with an increased risk of EH compared to GSTT1-present/GSTM1-present carriers (OR 6.75; 95% CI 3.4–13.2; p < 0.0001). Conclusion This study showed that the GSTT1-null alone or in interaction with GSTM1-present or GSTM1-null was associated with a higher risk of hypertension. Moreover, the GSTM1-null seems to be associated with the age of onset of hypertension