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Fan Lu

Publications and source records attributed to Fan Lu.

At least 19 recordsLinked to original sources
PubMed2026

Retinal microstructural alterations as early phenotypes of depression in radiogenomics analysis.

BACKGROUND: With the increasing prevalence of depression, there is an urgent clinical need for early screening in depression. The retina offers a promising window for early screening in depression due to its rapid, non-invasive, objective, eye-brain correlated characteristics, but previous research has yielded conflicting alterations in retinal microstructure in depression. METHODS: We screened retinal optical coherence tomography and brain magnetic resonance imaging data in the UK Biobank to enroll 23,225 participants for retinal study of depression occurrence, and 1475 participants for the eye-brain association study. We also used genetic data (ID: ebi-a-GCST90014267 and ukb-d-20,448) from the Integrative Epidemiology Unit Open Genome-Wide Association Study for Mendelian randomization analysis. We used Cox regression to assess the association between retinal microstructure and depression risk, Mendelian randomization to infer causality, and mediation analysis to explore retina-brain pathway association. RESULTS: The Cox regression analysis showed that retinal ganglion cell-inner plexiform layer (GCIPL) thickness remained a significant predictor of depression. The Mendelian randomization analysis indicated a positive statistical association between GCIPL thickness and depression. Moreover, there was a significant positive correlation (all p&#xa0;<&#xa0;0.001) between the volume of specific depression-related brain regions and the GCIPL thickness. Adjusting for age, sex, and head size, the mediation analysis provided preliminary evidence for a potential anatomical pathway linking retinal GCIPL thickness to depression-related brain regions through primary visual cortex and secondary visual cortex volumes. CONCLUSION: Thickened retinal GCIPL is a potential early phenotype of depression and has a potential association pathway with depression-related brain regions using a radiogenomics approach.

Humans↗
PubMed2026

Machine Learning-Driven Prediction of Coronary Artery Disease Risk Based on UK Biobank Plasma Proteomics.

BACKGROUND: Coronary artery disease (CAD) is a leading global cause of mortality, yet the predictive accuracy of conventional risk models is limited. Here, we integrate conventional risk factors, polygenic risk scores, and large-scale proteomics to develop a unified model for enhanced CAD risk prediction. METHODS: Using data from UK Biobank, participants with plasma proteomics and genetic risk data were included after excluding prevalent CAD. Participants from England were split into training (n=32&#x2009;330) and internal validation (n=13&#x2009;857) sets, and Scotland/Wales participants formed an external validation set (n=5775). Incident CAD was ascertained from linked health records. A 202-protein proteomic risk score was derived by least absolute shrinkage and selection operator Cox regression, and CatBoost models were trained using conventional risk factors alone and with incremental addition of polygenic risk scores and protein proteomic risk scores; Shapley Additive Explanations-guided forward selection identified a compact protein panel. RESULTS: Across cohorts, the median age was 58&#x2009;years and &#x223c;45% were men. Protein proteomic risk score was dose-dependently associated with CAD risk. Compared with conventional risk factors alone, integrating polygenic risk scores and protein proteomic risk scores improved discrimination, with the area under the curve increasing from 0.750 (95% CI, 0.732-0.767) to 0.789 (95% CI, 0.772-0.805) in internal validation and from 0.717 (95% CI, 0.683-0.750) to 0.762 (95% CI, 0.732-0.791) in external validation. A 9-protein panel (GDF15 [growth differentiation factor 15], MMP12 [matrix metalloproteinase 12], NPPB [natriuretic peptide B], PGF [placental growth factor], REN [renin], ADGRG2 [adhesion G-protein coupled receptor], ACE2 [angiotensin-converting enzyme 2], CDCP1 [CUB domain-containing protein 1], CXCL17 [C-X-C motif chemokine ligand 17)]) captured most proteomic predictive information. CONCLUSIONS: Our findings demonstrate that integrating conventional risk factors, polygenic risk scores, and proteomic data improves CAD risk prediction. This study highlights the utility of proteomics in precision cardiovascular medicine and simplified risk stratification tools.

Humans↗
PubMed2006

Bacisubin, an antifungal protein with ribonuclease and hemagglutinating activities from Bacillus subtilis strain B-916.

An antifungal protein, with a molecular mass of 41.9 kDa, and designated as bacisubin, was isolated from a culture of Bacillus subtilis strain B-916. The isolation procedure consisted of ion exchange chromatography on DEAE-Sepharose Fast Flow, and fast protein liquid chromatography on Phenyl Sepharose 6 Fast Flow and hydroxyapatite columns. The protein was adsorbed on all three chromatographic media. Bacisubin exhibited inhibitory activity on mycelial growth in Magnaporthe grisease, Sclerotinia sclerotiorum, Rhizoctonia solani, Alternaria oleracea, A. brassicae and Botrytis cinerea. The IC50 values of its antifungal activity toward the last four fungal species were 4.01 microM, 0.087 microM, 0.055 microM and 2.74 microM, respectively. Bacisubin demonstrated neither protease activity, nor protease inhibitory activity. However, it manifested ribonuclease and hemagglutinating activities.

Amino Acid Sequence↗
PubMed2006

[Study of Papaver somniferum cultivars identification by TD-RAPD technique].

OBJECTIVE: The feasibility of Papaver somniferum L. cultivars identification was explored by TD-RAPD technique. METHOD: Genomic DNA was extracted by improved CTAB method. One sample of species from Papaver somniferum L in xishuangbanna area. was studied by using TD-RAPD method. RESULT: We established an optimal method of extracting genomic DNA. Six primers were picked out from 10 primers. CONCLUSION: TD-RAPD could be applied to researches of molecular marker of Papaver somniferum L. TD-RAPD technique provide a method to constitute DNA database of Papaver somniferum L. and conclude the source of opium poppy.

DNA Primers↗
PubMed2006

Leber's hereditary optic neuropathy is associated with the mitochondrial ND6 T14484C mutation in three Chinese families.

We report here the clinical, genetic, and molecular characterization of three Chinese families with maternally transmitted Leber's hereditary optic neuropathy (LHON). Clinical and genetic evaluations revealed the variable severity and age-of-onset in visual impairment in these families. In the affected matrilineal relatives, the loss of central vision is bilateral, the fellow eye becoming affected either simultaneously (45%) or sequentially (55%). The penetrances of vision loss in these pedigrees were 27%, 50%, and 60%, respectively. The age-at-onset of vision loss in these families was 14, 19, and 24 years, respectively. Furthermore, the ratios between affected male and female matrilineal relatives were 1:1, 1:1.2, and 1:2, respectively. Mutational analysis of mitochondrial DNA revealed the presence of homoplasmic ND6 T14484C mutation, which has been associated with LHON. The incomplete penetrance and phenotypic variability implicate the involvement of nuclear modifier gene(s), environmental factor(s) or mitochondrial haplotype(s) in the phenotypic expression of the LHON-associated T14484C mutation in these Chinese pedigrees.

China↗
PubMed2006

Normal development of refractive state and ocular dimensions in guinea pigs.

PURPOSE: This study investigated changes in refraction, corneal curvature, axial components and weight of posterior sclera in guinea pig eyes during the normal development from birth. METHODS: Sixty-four guinea pigs were assigned to eight groups (n=8 each). Each group underwent a series of ocular measurements at one of the eight time-points (0, 1, 2, 3, 5, 7, 9 and 11 weeks), including refraction (streak retinoscopy), corneal radius of curvature (CRC; keratometry), anterior segment length (AS: corneal thickness and depth of the anterior chamber), thickness of the crystalline lens (CL), vitreous chamber length (VC; all A-scan ultrasonography) and dry weight of a circular 6mm diameter punch in the posterior sclera (electronic balance). Results of all the measurements were statistically compared between right eye and left eye, male and female and among different age groups. Artifacts of retinoscopy due to small eye artifact were also estimated at different ages. RESULTS: The refraction in guinea pig eyes was +5.22+/-0.23 D (Mean, SE) at birth. This value decreased rapidly during the first 3 weeks followed by a slow decline. The overall decrease in refraction was highly significant from birth to 11 weeks (p<0.001 one way ANOVA). The small eye artifact was approximately 4.00 D at birth, which reduced to 2.76 D at 11 weeks. The guinea pig eyes were emmetropic by 3 weeks of age when the small eye artifact was taken into account. The CRC (3.24+/-0.01 mm at birth), AS (1.20+/-0.01 mm at birth), CL (2.72+/-0.03 mm at birth) and VC (3.28+/-0.01 mm at birth) increased within the first 3 weeks despite a transient decrease in the CRC within the first week. The increase in CRC, CL and VC continued after 3 weeks, however, the AS remained constant after this age. The increase in VC was better correlated to the decline of hyperopia (R(2)=0.70) than the other components (R(2)=0.33-0.39). Dry weight of the posterior sclera increased linearly from birth (p<0.001 between any two close time-points from 3 to 9 weeks) and had a moderately linear correlation with the VC (R(2)=0.60). There were no significant differences between the right eye and left eye or between male and female in all the measurements. CONCLUSIONS: In guinea pigs, the hyperopia present at birth rapidly reduces to emmetropia within the first 3 weeks of age. The emmetropization process in guinea pigs is mainly related to the increase in the vitreous chamber length. This relationship in guinea pigs is similar to that in chickens, tree shrews, primates and humans. The axial development of the vitreous chamber in guinea pigs appears to be associated with tissue growth of the posterior sclera.

Animals↗
PubMed2006

The mitochondrial tRNA(Thr) A15951G mutation may influence the phenotypic expression of the LHON-associated ND4 G11778A mutation in a Chinese family.

We report here the characterization of a three-generation Han Chinese family with Leber's hereditary optic neuropathy (LHON). This Chinese family exhibited high penetrance and expressivity of visual impairment. The average age-of-onset was 19 years in this family. All male and 33% female matrilineal relatives in this Chinese family developed visual loss with a wide range of severity, ranging from blindness to normal vision. Sequence analysis of the complete mitochondrial DNA in this pedigree revealed the presence of the ND4 G11778A mutation and 40 other variants, belonging to the Asian haplogroup D4. The G11778A mutation is present at homoplasmy in matrilineal relatives of this Chinese family. Of other variants, the homoplasmic A15951G mutation is of special interest as it is located adjacent to 3' end, at conventional position 71 of tRNA(Thr). The adenine (A71) at this position of tRNA(Thr), highly conserved from bacteria to human mitochondria, has been implicated to be important for tRNA identity and pre-tRNA processing. In fact, the significant reduction of the steady-state levels in tRNA(Thr) was observed in cells carrying both the A15951G and G11778A mutations but not cells carrying only G11778A mutation. Thus, the A15951G mutation most probably leads to a failure in mitochondrial tRNA metabolism, worsening the mitochondrial dysfunction associated with the primary G11778A mutation. These imply that the tRNA(Thr) A15951G mutation may have a potential modifier role in increasing the penetrance and expressivity of the primary LHON-associated G11778A mutation in this Chinese family.

Adult↗
PubMed2006

Transcriptional up-regulation of restin by all-trans retinoic acid through STAT1 in cancer cell differentiation process.

RESTIN, a member of the melanoma-associated antigen superfamily, is a nuclear protein induced by atRA (all-trans retinoic acid) in HL60 cells. HeLa cells stably transfected with restin results in G1 cell cycle arrest. How this gene is regulated by atRA in the cell differentiation process is still unclear. In this study, we observed that up-regulation of restin was present during the atRA-induced HL60 cell differentiation process, suggesting the functional relevance between RESTIN and atRA-induced cellular effects. In order to further define the transcriptional regulation of restin by atRA, we analyzed the promoter region of restin. About 2.1kb 5' flanking sequence of this gene was cloned into vector pGL3 and its core promoter region was identified through systemic deletions. Interestingly, restin promoter containing several potential consensus-binding sites of STAT-1alpha was activated by atRA in ER(+) MCF-7 cells but not in ER(-) MDA-MB-231 cells, over-expression of STAT-1alpha in latter rescued the activation effect of restin promoter in response to atRA and IFNgamma. Our evidence supported that STAT-1alpha plays an important role in the atRA-induced transcriptional up-regulation of restin, which was associated with the atRA-induced HL60 cell differentiation and potentially mediated the downstream effects of atRA signal pathway via STAT-1alpha in some cancer cells.

Antigens, Neoplasm↗
PubMed2006

Construction and activity assay of the activating transcription factor 3 reporter vector pATF/CRE-luc.

Activating transcription factor 3 (ATF3), a member of the activating transcription factor/cAMP responsive element binding protein (ATF/CREB) family of transcription factors, is induced by many physiological stresses. To investigate the activity of ATF/CREB in cells with physiological stresses, we developed a practical reporter vector, the plasmid pATF/CRE-luc, bearing activating transcription factor/cAMP responsive element (ATF/CRE) binding sites. This plasmid was constructed by inserting three repeats of the ATF/CRE binding element into the plasmid pG5luc, replacing the GAL-4 binding sites. The plasmids pACT/ATF3 and pATF/CRE-luc were transfected into HeLa and NIH3T3 cells, respectively, and the results showed that the expression of luciferase was increased in a dose-dependent manner on plasmid pACT/ATF3. The data suggested that the plasmid pATF/CRE-luc could be used as a sensitive and convenient reporter system of ATF3 activity.

Activating Transcription Factor 3↗
PubMed2006

The novel A4435G mutation in the mitochondrial tRNAMet may modulate the phenotypic expression of the LHON-associated ND4 G11778A mutation.

PURPOSE: To investigating the role of mitochondrial haplotypes in the development of Leber's hereditary optic neuropathy (LHON) associated with the ND4 G11778A mutation in Chinese families. METHODS: A three-generation Chinese family with LHON was studied by clinical and genetic evaluation as well as molecular and biochemical analysis of mitochondrial (mt)DNA. RESULTS: This family exhibits a high penetrance and expressivity of visual impairment. The average age at onset was 13.9 years in this family. Of the family members, 86% of the male and 29% of the female matrilineal relatives had visual loss, with a wide range of severity, from blindness to nearly normal vision. Molecular analysis of mtDNA identified the homoplasmic ND4 G11778A mutation and 35 other variants, belonging to the Asian haplogroup D5. Of other variants, the novel homoplasmic A4435G mutation absent in 164 Chinese controls is localized at 3' end adjacent to the anticodon, at conventional position 37 (A37), of tRNAMet. The adenine (A37) at this position of tRNAMet is extraordinarily conserved from bacteria to human mitochondria. This modified A37 was shown to contribute to the high fidelity of codon recognition and to the structural formation and stabilization of functional tRNAs. In fact, the significant reduction of the steady state levels in tRNAMet was observed in cells carrying the both the A4435G and G11778A mutations but not cells carrying only the G11778A mutation. Thus, a failure in mitochondrial tRNA metabolism, caused by the A4435G mutation, may worsen the mitochondrial dysfunction associated with the primary G11778A mutation. CONCLUSIONS: The novel tRNAMet A4435G mutation has a potential modifier role in increasing the penetrance and expressivity of the primary LHON-associated G11778A mutation in this Chinese family.

Adolescent↗
PubMed2006

[Fusion expression, purification and bioactivity detection of human defensinalpha (HDalpha)].

AIM: To obtain recombinant human defensin alpha(HDalpha) and detect its biological activity, so as to facilitate further research. METHODS: The HDalpha gene fragment with hydroxylamine cleavage site was synthesized, and then cloned into pBV220-IL-4 vector to construct pBV220-IL-4-HDalpha. The constructed vector which was confirmed to be correct by sequencing was transformed into E.coli DH5alpha and the IL-4-HDalpha fusion protein was expressed under temperature induction. After fusion protein was cleaved to remove IL-4 by hydroxylamine, purification and renaturation was performed. HDalpha's characteristics were identified by SDS-PAGE and bioactivity detection. RESULTS: After temperature induction, the expressed fusion protein which accounted for about 20% of total bacterial protein existed mainly in the form of inclusion body. After cleaving by hydroxylamine, the purity of obtained HDalpha was about 99.8%. Bacteriostatic test and clone forming test showed that recombinant HDalpha could obviously inhibit the growth of bacteria. CONCLUSION: The recombinant expression plasmid for HDalpha gene has been constructed successfully and obtained engineering bacteria can stably express target protein. Furthermore, techniques of purification and renaturation was set out, which lays the foundation for further functional study and application of HDalpha.

Endostatins↗
PubMed2005

Leber's hereditary optic neuropathy is associated with the mitochondrial ND4 G11696A mutation in five Chinese families.

We report here the clinical, genetic, and molecular characterization of five Chinese families with Leber's hereditary optic neuropathy (LHON). Clinical and genetic evaluations revealed the variable severity and age-of-onset in visual impairment in these families. Strikingly, there were extremely low penetrances of visual impairment in these Chinese families. Sequence analysis of the complete mitochondrial genomes in these pedigrees showed the distinct sets of mtDNA polymorphism, in addition to the identical ND4 G11696A mutation associated with LHON. Indeed, this mutation is present in homoplasmy only in the maternal lineage of those pedigrees but not other members of these families. In fact, the occurrence of the G11696A mutation in these several genetically unrelated subjects affected by visual impairment strongly indicates that this mutation is involved in the pathogenesis of visual impairment. Furthermore, the N405D in the ND5 and G5820A in the tRNA(Cys), showing high evolutional conservation, may contribute to the phenotypic expression of G11696A mutation in the WZ10 pedigree. However, there was the absence of functionally significant mtDNA mutations in other four Chinese pedigrees carrying the G11696A mutation. Therefore, nuclear modifier gene(s) or environmental factor(s) may play a role in the phenotypic expression of the LHON-associated G11696A mutation in these Chinese pedigrees.

Adolescent↗
PubMed2005

Axial myopia induced by a monocularly-deprived facemask in guinea pigs: A non-invasive and effective model.

This study evaluated the efficacy of a facemask, a non-invasive and potentially more reliable method, in inducing axial myopia in guinea pigs. Thirty-six animals were randomly assigned to 3 groups: MDF (monocularly-deprived facemask, n=6), lid-suture (eyelids sutured monocularly, n=24) and normal control (free of form deprivation, n=6). All the groups underwent biometric measurement (refraction, corneal curvature and axial length) prior to the experiment. All animals in the MDF group underwent biometric measurement at each of the 4 timepoints (2, 4, 6 and 8 weeks of form deprivation). In the lid-sutured group, the animals were randomly assigned to 4 subgroups (n=6 each) and each subgroup underwent biometric measurement at one of the timepoints matching those of the MDF group. In the normal control group, all animals underwent biometric measurement at each of the timepoints matching those of the 2 experimental groups. Placement of a facemask on an animal took approximately 10 sec and all the facemasks remained in place at all timepoints. The procedure of lid-suture took at least 20 min for an animal and rupture of the sutures occurred in 50% of the animals after 4 weeks. The MDF eyes developed myopia from -2.21+/-2.11D (Mean+/-s.d.) at 2 weeks to -4.38+/-2.14 at 8 weeks (p<0.05 at all timepoints, compared to the contralateral eyes) with a lengthening of the vitreous chamber from 0.17+/-0.05 mm at 2 weeks to 0.29+/-0.12 mm at 8 weeks (p<0.01 at all timepoints, compared to the contralateral eyes). The lid-sutured eyes developed myopia from -2.38+/-1.21D at 2 weeks to -4.75+/-1.39D at 8 weeks (p<0.05 at all timepoints, compared to the contralateral eyes) with a lengthening of the vitreous chamber from 0.13+/-0.02 mm at 2 weeks to 0.30+/-0.10 mm at 8 weeks (p<0.05 at 2, 4, 8 weeks, but >0.05 at 6 weeks, compared to the contralateral eyes) and an increase in the radius of the corneal curvature (0.20+/-0.07 mm at 4 weeks, p<0.01; 0.17+/-0.05 mm at 8 weeks, p<0.05; compared to the contralateral eyes). Both the MDF and lid-sutured groups had a similar development in myopia and vitreous length (MDF vs lid-suturing: p>0.05 at all timepoints, one-way ANOVA with Bonferroni correction). This development was significantly faster than in the normal control group (MDF or lid-suture vs normal control: p<0.05 to <0.01 from 2 to 8 weeks, one-way ANOVA with Bonferroni correction). The radius of corneal curvature in the lid-sutured group was significantly greater than in either the MDF group or the normal control group since 4 weeks of form deprivation (p<0.05, one-way ANOVA with Bonferroni correction). Treatment with MDFs is as effective as the lid-suture in inducing axial myopia in guinea pigs. This method is non-invasive and allows evaluation of the same group of animals at different timepoints so that the number of animals required could be minimized without affecting the accuracy of the results.

Animals↗
PubMed2005

Hepatitis C virus infection in former commercial plasma/blood donors in rural Shanxi Province, China: the China Integrated Programs for Research on AIDS.

BACKGROUND: Unsafe practices during illegal plasma donation in the late 1980s and early 1990s spread bloodborne infections in central China. METHODS: A cross-sectional survey of a random sample of 538 adult residents of 12 villages in rural Shanxi Province, where there had been an illegal commercial plasma-collection center, was conducted in 2003. Structured questionnaires were administered, and blood samples were tested for hepatitis C virus (HCV) antibodies. RESULTS: HCV seroprevalence rates were 8.2% in all subjects, 27.7% in former commercial plasma/blood donors, and 2.6% in nondonors. Selling blood or plasma was the strongest independent predictor of HCV seropositivity (odds ratio [OR], 14.4 [95% confidence interval {CI}, 7.1-31.6]). A history of blood transfusion was also independently associated with HCV seropositivity (OR, 8.3 [95% CI, 2.1-32.0]). Plasma donors had a higher risk of being HCV seropositive than did whole-blood donors (OR, 7.6 [95% CI, 2.9-20.9]), and female donors had a lower risk than did male donors (OR, 0.32 [95% CI, 0.12-0.80]). The strength of the association between selling blood and HCV seropositivity was weaker when plasma donors were excluded (OR, 8.0 vs. 14.4). CONCLUSIONS: Unsafe practices during illegal plasma donation led to a high risk of HCV seropositivity for donors during the 1980s and 1990s. Failure to screen for HCV increased the risk of seropositivity for transfusion recipients during this same period. China has taken steps to halt illegal plasma collection and to improve blood-banking methods. However, there will be an ongoing challenge to care for patients with HCV infection, even as its incidence decreases.

Adult↗
PubMed2005

Development of the human superior colliculus and the retinocollicular projection.

We have used carbocyanine dye tracing from the brachium of the superior colliculus in conjunction with Nissl staining and immunohistochemistry to GAP-43 and calretinin to study the development of retinal projections to the superior colliculus in 17 human embryos and fetuses aged from 8 to 28 weeks. Lamination of the superior colliculus begins to emerge by 11 weeks, and by 16 weeks all seven layers of the mature superior colliculus are visible. Fibres immunoreactive to GAP-43 were seen at 13 weeks in the most superficial layers. By 19 weeks, GAP-43 immunoreactivity was present in the stratum opticum as well as the deeper fibres layers, indicating the development of fibre pathways following those laminae. Carbocyanine dye tracing of retinocollicular projections showed extensive rostrocaudally running unbranched fibres in the superficial superior colliculus at 12 weeks. Shortly after this (13 weeks), retinocollicular fibres penetrate the deeper collicular layers and branching becomes apparent. We also saw occasional retrogradely labelled somata following DiI insertion into the superior brachium. Our findings indicate that development of the human superior colliculus and its connections is largely complete by 20 weeks. This would suggest that functional capacity of the human superior colliculus should also be mature by the middle of gestation.

Calbindin 2↗
PubMed2005

Framework for kernel regularization with application to protein clustering.

We develop and apply a previously undescribed framework that is designed to extract information in the form of a positive definite kernel matrix from possibly crude, noisy, incomplete, inconsistent dissimilarity information between pairs of objects, obtainable in a variety of contexts. Any positive definite kernel defines a consistent set of distances, and the fitted kernel provides a set of coordinates in Euclidean space that attempts to respect the information available while controlling for complexity of the kernel. The resulting set of coordinates is highly appropriate for visualization and as input to classification and clustering algorithms. The framework is formulated in terms of a class of optimization problems that can be solved efficiently by using modern convex cone programming software. The power of the method is illustrated in the context of protein clustering based on primary sequence data. An application to the globin family of proteins resulted in a readily visualizable 3D sequence space of globins, where several subfamilies and subgroupings consistent with the literature were easily identifiable.

Algorithms↗
PubMed2005

Clinical evaluation and mitochondrial DNA sequence analysis in three Chinese families with Leber's hereditary optic neuropathy.

We report here the clinical, genetic, and molecular characterization of three Chinese families (WZ4, WZ5, and WZ6) with Leber's hereditary optic neuropathy (LHON). Clinical and genetic evaluations revealed the variable severity and age-of-onset in visual impairment in these families. Penetrances of visual impairment in these Chinese families were 33.3%, 35.7%, and 35.5%, respectively, with an average 34.8%. Furthermore, the average age-at-onset in those Chinese families was 17, 20, and 18 years. In addition, the ratios between affected male and female matrilineal relatives in these Chinese families were 3:0, 1:1, and 1.2:1, respectively. Sequence analysis of the complete mitochondrial genomes in these pedigrees showed the distinct sets of mtDNA polymorphism, in addition to the identical G11778A mutation associated with LHON in many families. The fact that mtDNA of those pedigrees belonged to different haplogroups F1, D4, and M10 suggested that the G11778A mutation occurred sporadically and multiplied through evolution of the mtDNA in China. However, there was the absence of functionally significant mutations in tRNA and rRNAs or secondary LHON mutations in these Chinese families. The I187T mutation in the ND1, the S99A mutation in the A6, the V254I in CO3, and I58V in ND6 mutation, showing high evolutional conservation, may contribute to the phenotypic expression of the G11778A mutation in the WZ6 pedigree. By contrast, none of mtDNA variants are evolutionarily conserved and implicated to have significantly functional consequence in WZ4 and WZ5 pedigrees. Apparently, these variants do not have a potential modifying role in the development of visual impairment associated with G11778A mutation in those two families. Thus, nuclear modifier gene(s) or environmental factor(s) seem to account for the penetrance and expressivity of LHON in these three Chinese families carrying the G11778A mutation.

Adolescent↗