The association between glucose-6-phosphate dehydrogenase deficiency and abnormal blood pressure among prepregnant reproductive-age Chinese females.

The morbidity of hypertension is increasing among young adults worldwide, and glucose-6-phosphate dehydrogenase (G6PD) deficiency is a high-prevalence genetic disease. We investigated whether G6PD deficiency was associated with abnormal blood pressure (including elevated blood pressure and hypertension) among prepregnant reproductive-age females. We conducted a cross-sectional study in Shenzhen, which included 154 917 females aged 20-49 who participated in the National Free Pre-conception Check-up Projects supported by the Chinese government. After adjusting for confounding factors, the odds ratios (ORs) for the effects of G6PD deficiency on elevated blood pressure and hypertension were 1.18 (95% confidence interval (CI): 1.03-1.35) and 1.11 (95% CI: 1.00-1.23), respectively. Moreover, the association between G6PD deficiency and abnormal blood pressure was statistically significant for systolic blood pressure (SBP) but not significant for diastolic blood pressure (DBP). The multivariable-adjusted ORs for females with G6PD deficiency in the SBP 120-139 mm Hg and SBP ≥ 140 mm Hg groups were 1.10 (95% CI: 1.00-1.21) and 1.75 (95% CI: 1.25-2.42), respectively, while the multivariable-adjusted ORs for females with G6PD deficiency in the DBP 80-89 mm Hg and DBP ≥ 90 mm Hg groups were 1.09 (95% CI: 0.98-1.21) and 0.89 (95% CI: 0.66-1.19), respectively. Subgroup analyses showed similar results. The findings of this study underscored that reproductive-age females with a G6PD deficiency had a higher risk of elevated blood pressure and hypertension. Therefore, females with G6PD deficiency combined with elevated blood pressure or hypertension were high-risk populations during prepregnancy and pregnancy periods. Early intervention and collaborative management approaches should be explored to reduce the burden of these two diseases and improve maternal and child health.

Exome sequencing identifies a novel mutation of the GDI1 gene in a Chinese non-syndromic X-linked intellectual disability family.

X-linked intellectual disability (XLID) has been associated with various genes. Diagnosis of XLID, especially for non-syndromic ones (NS-XLID), is often hampered by the heterogeneity of this disease. Here we report the case of a Chinese family in which three males suffer from intellectual disability (ID). The three patients shared the same phenotype: no typical clinical manifestation other than IQ score ≤ 70. For a genetic diagnosis for this family we carried out whole exome sequencing on the proband, and validated 16 variants of interest in the genomic DNA of all the family members. A missense mutation (c.710G > T), which mapped to exon 6 of the Rab GDP-Dissociation Inhibitor 1 (GDI1) gene, was found segregating with the ID phenotype, and this mutation changes the 237th position in the guanosine diphosphate dissociation inhibitor (GDI) protein from glycine to valine (p. Gly237Val). Through molecular dynamics simulations we found that this substitution results in a conformational change of GDI, possibly affecting the Rab-binding capacity of this protein. In conclusion, our study identified a novel GDI1 mutation that is possibly NS-XLID causative, and showed that whole exome sequencing provides advantages for detecting novel ID-associated variants and can greatly facilitate the genetic diagnosis of the disease.

Exome sequencing identifies a novel mutation of the GDI1 gene in a Chinese non-syndromic X-linked intellectual disability family

Abstract X-linked intellectual disability (XLID) has been associated with various genes. Diagnosis of XLID, especially for non-syndromic ones (NS-XLID), is often hampered by the heterogeneity of this disease. Here we report the case of a Chinese family in which three males suffer from intellectual disability (ID). The three patients shared the same phenotype: no typical clinical manifestation other than IQ score ≤ 70. For a genetic diagnosis for this family we carried out whole exome sequencing on the proband, and validated 16 variants of interest in the genomic DNA of all the family members. A missense mutation (c.710G > T), which mapped to exon 6 of the Rab GDP-Dissociation Inhibitor 1 (GDI1) gene, was found segregating with the ID phenotype, and this mutation changes the 237th position in the guanosine diphosphate dissociation inhibitor (GDI) protein from glycine to valine (p. Gly237Val). Through molecular dynamics simulations we found that this substitution results in a conformational change of GDI, possibly affecting the Rab-binding capacity of this protein. In conclusion, our study identified a novel GDI1 mutation that is possibly NS-XLID causative, and showed that whole exome sequencing provides advantages for detecting novel ID-associated variants and can greatly facilitate the genetic diagnosis of the disease.

A Novel Potentially Causative Variant of NDUFAF7 Revealed by Mutation Screening in a Chinese Family With Pathologic Myopia.

Purpose: Pathologic myopia described as myopia accompanied by severe deformation of the eye besides excessive elongation of eye, is usually a genetic heterogeneous disorder characterized by extreme, familial, early-onset vision loss. However, the exact pathogenesis of pathologic myopia remains unclear. In this study, we screened a Han Chinese family with pathologic myopia to identify the causative mutation and explore the possible pathogenic mechanism based on evaluation of the biological functions of the mutation. Methods: We identified the mutations in a family with pathologic myopia by single nucleotide polymorphism array combined with short tandem repeat microsatellite marker analysis and exome sequencing. Mutations were validated among family members by direct Sanger sequencing. The subcellular localization of the protein variant was investigated by immunofluorescence, and the stability of the mutant protein was determined by immunoblotting. Intracellular levels of adenosine triphosphate and reactive oxygen species and complex I activity were measured by traditional biochemical methods to determine the functional role of the disease-associated mutation. Results: The novel missense mutation: c.798C>G (p.Asp266Glu) in NDUFAF7, cosegregated with the disease and the resulting amino acid substitution affected a highly conserved residue in its protein. The mutation D266E in NDUFAF7 impaired complex I activity, which resulted in decreased ATP levels in cultured cells. Conclusions: We propose that the heterozygous mutation (c.798C>G) in NDUFAF7 may contribute to the pathogenesis of pathologic myopia, possibly by interfering with the phototransduction cascade. Mitochondrial dysfunction during eye development may lead to pathologic myopia.