Whole exome sequencing and trio analysis to broaden the variant spectrum of genes in idiopathic hypogonadotropic hypogonadism / 亚洲男科学杂志(英文版)

Dozens of genes are associated with idiopathic hypogonadotropic hypogonadism (IHH) and an oligogenic etiology has been suggested. However, the associated genes may account for only approximately 50% cases. In addition, a genomic systematic pedigree analysis is still lacking. Here, we conducted whole exome sequencing (WES) on 18 unrelated men affected by IHH and their corresponding parents. Notably, one reported and 10 novel variants in eight known IHH causative genes (AXL, CCDC141, CHD7, DMXL2, FGFR1, PNPLA6, POLR3A, and PROKR2), nine variants in nine recently reported candidate genes (DCAF17, DCC, EGF, IGSF10, NOTCH1, PDE3A, RELN, SLIT2, and TRAPPC9), and four variants in four novel candidate genes for IHH (CCDC88C, CDON, GADL1, and SPRED3) were identified in 77.8% (14/18) of IHH cases. Among them, eight (8/18, 44.4%) cases carried more than one variant in IHH-related genes, supporting the oligogenic model. Interestingly, we found that those variants tended to be maternally inherited (maternal with n = 17 vs paternal with n = 7; P = 0.028). Our further retrospective investigation of published reports replicated the maternal bias (maternal with n = 46 vs paternal with n = 28; P = 0.024). Our study extended a variant spectrum for IHH and provided the first evidence that women are probably more tolerant to variants of IHH-related genes than men.

Role of heteroplasmic mutations in the mitochondrial genome and the ID4 gene promoter methylation region in the pathogenesis of chronic aplastic anemia in patients suffering from Kidney yin deficiency / 中国结合医学杂志

<p><b>OBJECTIVE</b>To analyze changes in gene amplification in the mitochondrial genome and in the ID4 gene promoter methylation region in patients with chronic aplastic anemia (CAA) suffering from Kidney (Shen) yin deficiency or Kidney yang deficiency.</p><p><b>METHODS</b>Bone marrow and oral epithelium samples were collected from CAA patients with Kidney yin deficiency or Kidney yang deficiency (20 cases). Bone marrow samples were collected from 20 healthy volunteers. The mitochondrial genome was amplified by polymerase chain reaction (PCR), and PCR products were used for sequencing and analysis.</p><p><b>RESULTS</b>Higher mutational rates were observed in the ND1-2, ND4-6, and CYTB genes in CAA patients suffering from Kidney yin deficiency. Moreover, the ID4 gene was unmethylated in bone marrow samples from healthy individuals, but was methylated in some CAA patients suffering from Kidney yin deficiency (positive rate, 60%) and Kidney yang deficiency (positive rate, 55%).</p><p><b>CONCLUSIONS</b>These data supported that gene mutations can alter the expression of respiratory chain enzyme complexes in CAA patients, resulting in energy metabolism impairment and promoting the physiological and pathological processes of hematopoietic failure. Functional impairment of the mitochondrial respiration chain induced by gene mutation may be an important reason for hematopoietic failure in patients with CAA. This change is closely related to maternal inheritance and Kidney yin deficiency. Finally, these data supported the assertion that it is easy to treat disease in patients suffering from yang deficiency and difficult to treat disease in patients suffering from yin deficiency.</p>

The relationship of visual prognosis and G11778A point mutation in Leber hereditary optic neuropathy / 中华实验眼科杂志

Background Leber hereditary optic neuropathy (LHON) is a disease characterized by maternal inheritance.A number of mitochondrial DNA (mtDNA) mutation has been thought to be associated with this disease.Objective This study was to investigate the clinical and molecular genetic properties of LHON in two Chinese families.Methods Forty subjects from two Chinese families with LHON were enrolled in Affiliated First Hospital of Zhengzhou University,including 28 maternal members (10 of these members are LHON and 12 controls from two families.All the participants had a complete ophthalmic examination including visual acuity,direct ophthalmoscopy,color sensation and visual evoked potentials.MtDNA was extract from the whole blood sample of all participants.PCR-DNA sequencing was performed to detect the point mutation of the G11778A,T14484C,and G3462A for each subject.Written informed consent was obtained from each subject prior to this study.Results Only G11778A point mutation was identified in all 28 maternal members from the two families.No point mutation of G11778A was identified in non-maternal members,and no point mutation of the T14484C and G3462A were found in the two families.Conclusions The inherited pattern of these two families shows typical clinical and genetic features of LHON.LHON patients with G1 1778A mutation have a poor prognosis of visual acuity.