AIM:To analyze the clinical phenotypes and genotypes of children with incontinentia pigmenti(IP)and enhance clinicians' understanding of the condition.METHODS: A family with IP diagnosed in February 2020 at the ophthalmology department of People's Hospital of Ningxia Hui Autonomous Region was enrolled. The proband and family members underwent comprehensive systemic and ocular examinations. Peripheral venous blood was collected for DNA extraction, followed by whole-exome sequencing and MLPA assay to identify pathogenic variants. Corresponding treatments were administered based on the severity of fundus lesions, and ocular clinical features and therapeutic outcomes were monitored during follow-up.RESULTS: The child in this study was a female, aged 8 years, with typical skin changes and scarring alopecia and dental abnormalities at the time of initial consultation. The results of genetic testing suggested that the child carried a heterozygous deletion of exons 4-10 of the IKBKG gene chrX:153440010-153446570del. The child had asymmetric lesions in both eyes, with severe lesions in the left eye, atrophy of the eyeballs, and ocular B-ultrasound suggesting structural disturbances in the eye, and neovascularization was seen in the peripheral retina of the right eye, and the patient was given laser photocoagulation treatment for the right eye, and no progression of retinopathy was detected during follow-up.CONCLUSION:Children with IP have different ocular clinical phenotypes, and retinal vasculopathy is the main change. Early screening and timely and standardized treatment are crucial for children diagnosed with IP.

Objective To investigate the relationship between serum levels of micro RNA(miR)-497-5p,fibroblast growth factor-2(FGF2)and brain-derived neurotrophic factor(BDNF),with cognitive dysfunction in Parkinson's disease(PD)patients.Methods From April 2022 to April 2024,86 PD patients(study group)treated in Wuhan Xinzhou District People's Hospital and 60 healthy individuals(control group)who underwent physical examination in Wuhan Xinzhou District People's Hospital were selected.Serum miR-497-5p levels were determined by real-time quantitative polymerase chain reaction(RT-qPCR),and serum FGF2 and BDNF levels were measured by enzyme linked immunosorbent assay(ELISA).Spearman was applied to analyze the correlation between serum miR-497-5p,FGF2,BDNF levels and montreal cognitive assessment(MoCA score).Logistic analysis was applied to analyze the factors influencing cognitive dysfunction in PD patients.Receiver operating characteristic(ROC)was applied to analyze the diagnostic value of serum miR-497-5p,FGF2 and BDNF for cognitive dysfunction in PD patients.Results The serum miR-497-5p(2.73±0.67)expression level in the study group was obviously increased than that in the control group(1.04±0.34),while the expression levels of FGF2(1.94±0.45ng/ml)and BDNF(8.31±2.44ng/ml)were obviously reduced than those in the control group(2.71±0.69ng/ml,12.81±3.07ng/ml),with significate differences(t=17.977,8.161,9.850,all P<0.05).Serum miR-497-5p was negatively correlated with MoCA score(r=-0.331,P<0.05),while FGF2 and BDNF levels were positively correlated with MoCA score(r=0.404,0.361,all P<0.05).Cognitive dysfunction group had significantly higher disease duration,FGF2,BDNF levels,and MoCA scores than the cognitively normal group.The course of disease and miR-497-5p levels in the cognitive dysfunction group were obviously higher than that in the normal cognitive function group,FGF2,BDNF levels,and MoCA scores in the cognitive dysfunction group were obviously lower than that in the normal cognitive function group(t=2.350～11.792,all P<0.05).The course of disease and serum miR-497-5p were risk factors for cognitive dysfunction in PD patients(Wald χ2=4.712,5.704,all P<0.05),while MoCA score,serum FGF2,and BDNF were protective factors for cognitive dysfunction in PD patients(Wald χ2=4.499,5.556,5.217,all P<0.05).The AUC and sensitivity of the combination of serum miR-497-5p,FGF2,and BDNF in PD patients with cognitive impairment were higher than those of individual diagnosis.The diagnostic effect of the combination of miR-497-5p,FGF2,and BDNF in PD patients with cognitive dysfunction was better than that of individual diagnosis,and the differences were statistically significant(Z=2.279,2.236,2.123,all P<0.05).Conclusion Elevated serum miR-497-5p level and decreased FGF2 and BDNF levels can increase the risk of cognitive dysfunction in PD patients,and the combination of the three has good diagnostic value for cognitive dysfunction in PD patients.

Objective To investigate the relationship between serum levels of micro RNA(miR)-497-5p,fibroblast growth factor-2(FGF2)and brain-derived neurotrophic factor(BDNF),with cognitive dysfunction in Parkinson's disease(PD)patients.Methods From April 2022 to April 2024,86 PD patients(study group)treated in Wuhan Xinzhou District People's Hospital and 60 healthy individuals(control group)who underwent physical examination in Wuhan Xinzhou District People's Hospital were selected.Serum miR-497-5p levels were determined by real-time quantitative polymerase chain reaction(RT-qPCR),and serum FGF2 and BDNF levels were measured by enzyme linked immunosorbent assay(ELISA).Spearman was applied to analyze the correlation between serum miR-497-5p,FGF2,BDNF levels and montreal cognitive assessment(MoCA score).Logistic analysis was applied to analyze the factors influencing cognitive dysfunction in PD patients.Receiver operating characteristic(ROC)was applied to analyze the diagnostic value of serum miR-497-5p,FGF2 and BDNF for cognitive dysfunction in PD patients.Results The serum miR-497-5p(2.73±0.67)expression level in the study group was obviously increased than that in the control group(1.04±0.34),while the expression levels of FGF2(1.94±0.45ng/ml)and BDNF(8.31±2.44ng/ml)were obviously reduced than those in the control group(2.71±0.69ng/ml,12.81±3.07ng/ml),with significate differences(t=17.977,8.161,9.850,all P<0.05).Serum miR-497-5p was negatively correlated with MoCA score(r=-0.331,P<0.05),while FGF2 and BDNF levels were positively correlated with MoCA score(r=0.404,0.361,all P<0.05).Cognitive dysfunction group had significantly higher disease duration,FGF2,BDNF levels,and MoCA scores than the cognitively normal group.The course of disease and miR-497-5p levels in the cognitive dysfunction group were obviously higher than that in the normal cognitive function group,FGF2,BDNF levels,and MoCA scores in the cognitive dysfunction group were obviously lower than that in the normal cognitive function group(t=2.350～11.792,all P<0.05).The course of disease and serum miR-497-5p were risk factors for cognitive dysfunction in PD patients(Wald χ2=4.712,5.704,all P<0.05),while MoCA score,serum FGF2,and BDNF were protective factors for cognitive dysfunction in PD patients(Wald χ2=4.499,5.556,5.217,all P<0.05).The AUC and sensitivity of the combination of serum miR-497-5p,FGF2,and BDNF in PD patients with cognitive impairment were higher than those of individual diagnosis.The diagnostic effect of the combination of miR-497-5p,FGF2,and BDNF in PD patients with cognitive dysfunction was better than that of individual diagnosis,and the differences were statistically significant(Z=2.279,2.236,2.123,all P<0.05).Conclusion Elevated serum miR-497-5p level and decreased FGF2 and BDNF levels can increase the risk of cognitive dysfunction in PD patients,and the combination of the three has good diagnostic value for cognitive dysfunction in PD patients.

Objective:To analyze the genotype of hereditary eye diseases with early-onset high myopia (eoHM) and its relationship with phenotype.Methods:The families with eoHM were collected in Ningxia Eye Hospital from January 2019 to June 2020.The medical records of the probands and their family members were inquired and recorded in detail, and the relevant ocular examinations were performed.Peripheral venous blood samples were collected from patients and their family members, and whole-genome DNA was extracted.Sequence capture sequencing technology was applied to screen for disease-causing gene mutations in probands.The detected suspected pathogenic variants were verified by Sanger sequencing and were analyzed by family cosegregation analysis.According to ACMG guidelines, the pathogenicity of novel variants was evaluated.The original literature about hereditary eye diseases with eoHM was searched to analyze the relationship between mutated genes and clinical phenotype.This study protocol adhered to the Declaration of Helsinki.All subjects or their guardians were informed of the purpose and procedure of the study and signed the informed consent form.The study protocol was approved by the Ethics Committee of the People's Hospital of Ningxia Hui Autonomous Region (No.2016018).Results:A total of 20 eoHM families were collected, among which pathogenic variants associated with inherited eye diseases were detected in 8 families.Of the 8 probands, two were diagnosed with familial exudative vitreoretinopathy, one with X-linked retinitis pigmentosa, one with congenital stationary nightblindness, one with Stickler syndrome, one with achromatopsia, one with Leber congenital amaurosis, and one with gyrate atrophy of the choroid and retina.The first diagnosis age of the 8 probands was 4-7 years old, and they were all diagnosed as high myopia, with a refractive status ≤-6.00 DS.Genetic tests showed that the 8 probands carried a heterozygous variant c. 313A>G (p.M105Val) in FZD4 gene, a heterozygous variant c. 14_15insAAGA (p.Asp5fs *) in TSPAN12 gene, a heterozygous frameshift variant c. 2234_2237del (p.Arg745fs) in RPGR gene, a compound heterozygous variant of c. 481C>T (p.Gln161Ter *) and c. 355>T (p.Arg119Cys *) in GPR179 gene, a frameshift variant c. 1659_1660insACGGTGACCCTGGCCGTCCTGG (p.Pro554fs *) in COL2A1 gene, a compound heterozygous variant of c. 1811C>T (p.Thr604Ile *) and c. 967G>A (p.Gly323Ser) in PDE6B gene, a compound heterozygous variant of c. 604_619delTCCACGGCACTCAGGG (p.Ser202fs *) and c. 995G>C (p.Arg332Pro) in GUCY2D gene, a homozygous variant c. 772C>T (p.Pro241Leu) in OAT gene.Seven of them were novel variants.Compared with the previous literature, the clinical and gene phenotypes of the 8 families were analyzed in detail in this study, which provided the basis for the diagnosis of hereditary eye diseases with eoHM. Conclusions:EoHM is closely related to some hereditary eye diseases, which may be the reason for the early diagnosis of children and an important clue for clinicians to detect potential hereditary eye diseases.Further clinical evaluations of ocular structure and function as well as genetic screening in children with eoHM are recommended.

Objective:To observe and analyze the gene mutation and clinical phenotype of patients with cone and rod dystrophy (CORD).Methods:A pedigree investigarion. Two CORD pedigrees including 2 patients and 6 family members were enrolled in Ningxia Eye Hospital of People' Hospital of Ningxia Hui Automous Region for this study. The patients were from 2 unrelated families, all of whom were probands. Take medical history with best-corrected visual acuity (BCVA), color vision, slit lamp microscopy, indirect ophthalmoscopy, fundus color photography, optical coherence tomography (OCT), autofluorescence (AF), fluorescein fundus angiography (FFA), electroretinogram (ERG). The peripheral venous blood of patients and their parents was collected, whole genome DNA was extracted, Trio whole genome exome sequencing was performed, Sanger verification and pedigree co-segregation were performed for suspected pathogenic mutation sites. According to the law of inheritance, family history was analyzed to establish its genetic type. Mutational loci pathogenicity was analyzed according to the American College of Medical Genetics (ACMG) guidelines and 4 online tools.Results:Two CORD families showed autosomal recessive inheritance. The proband of pedigree 1 was female, 49 years old. Binocular vision loss with photophobia lasted for 9 years and night blindness for 4 years. The BCVA of right eye and left eye were 0.03 and 0.06, respectively. The results of ERG showed that the amplitudes of dark adaptation 0.01 b-wave and dark adaptation 3.0 a-wave and b-wave in both eyes were slightly decreased, and the amplitudes of light adaptation 3.0 a-wave and b-wave were severely decreased. The proband of pedigree 2 was male, 30 years old. Vision loss in both eyes for 4 years. Denying a history of night blindness. The BCVA of right eye and left eye were 0.3 and 0.2, respectively. The results of ERG showed that the amplitudes of dark adaptation 0.01 b-wave and dark adaptation 3.0 a-wave and b-wave in both eyes were slightly decreased, and the amplitudes of light adaptation 3.0 a-wave and b-wave were severely decreased. The color of optic disc in both eyes was light red, the macular area was atrophic, the foveal reflection disappeared, and the peripheral retina was punctate pigmentation. The main fundus changes in 2 patients were macular atrophy. The proband of pedigree 1 carried compound heterozygous variations c.439-2A>G (M1) and c.676delT (p.F226fs) (M2) on CDHR1 gene. Her father and mother carried M2 and M1 heterozygous mutations, respectively. The proband of pedigree 2 carried compound heterozygous variations c.2665dupC (p.L889fs) (M3) and c.878T>C (p.L293P) (M4) on C2orf71 gene. His father and mother carried M4 and M3 heterozygous mutations, respectively. According to ACMG guidelines and on line tools, 4 variations were considered as pathogenic level. Conclusions:M1 and M2 of CDHR1 gene and M3 and M4 of C2orf71 gene are new pathogenic mutations of CORD. All patients presented with the clinical phenotype of decreased visual acuity and macular atrophy.

Objective:To identify 3 the disease-causing genes and mutations of Leber congenital amaurosis (LCA), and to study the correlation of phenotype and genotype.Methods:A retrospective study. Four LCA patients and seven family members who were diagnosed by eye examination in Ning Xia Eye Hospital of People's Hospital of Ningxia Hui Autonomous Region from January to December 2021 were included in the study. Four patients were from 3 unrelated families. Detailed collection of medical history and family history were received. Related ophthalmologic examination were collected and genomic DNA was extracted from peripheral blood. Whole-exome sequencing method was used for genetic diagnosis. The identified variant was confirmed with Sanger sequencing. Potential pathogenic mutation was analyzed using software and conserved domain analysis and performed co-separated analysis between the family member and the proband.Results:Of the 4 patients, 1 patient was males and 3 patients were females; the age was from 4 to 18 years. Nystagmus were seen in 3 cases, finger pressing eyes and night blindness was seen in 1 cases; electroretinogram showed 4 cases of extinction or near extinction. The foveal reflection was visible in all eyes, and there was no obvious abnormality in the peripheral retina. One eye had strong reflection signal with raised ellipsoid in macular area; two eyes had weak reflection signal faintly visible between retinal layers; 1 eye had increased blood vessel branches, peripheral retinal non-perfusion area with capillary leakage; annular strong autofluorescence in macular area 4 eyes. No obvious abnormality was found in the phenotypes of family members. Genetic testing showed that the proband of pedigree 1 (Ⅱ-1) was found a homozygous missense mutation in c.640A>T (p.C214S) (M1) of PRPH2 gene. The proband of pedigree 2 (Ⅱ-2) was found compound heterozygous mutation in c.1256G>A(p.R419Q) (M2) and c.1A>C (p.M1L) (M3) of TULP1 gene. The proband 3 (Ⅱ-1) and her sister (Ⅱ-2) were both found compound heterozygous mutation in c.1943T>C (p.L648P) (M4) and c.380C>T (p.P127L) (M5) of GUCY2D gene. The parents and sister (Ⅱ-1) of the proband in family 2 and the parents of the proband in family 3 were all carriers of the corresponding heterozygous variant. M1, M3, M4, M5 were novel mutations and unreported. The genotype and disease phenotype were co-segregated within the family. According to the analysis of pedigree and genetic testing results, all 3 families were autosomal recessive inheritance. The amino acid conservation analysis found that M1, M2, M3, M4, and M5 were highly conserved among species. The results of bioinformatics analysis were all pathogenic variants. Conclusions:PRPH2 gene M1, TULP1 gene M3, and GUCY2D gene M4, M5 were novel mutations and not been reported in the literature and database. This research expanded the gene mutation spectrum of LCA. The patients with LCA have available characterristics, including onset age, varying ocular fundus and severe visual impairment.

Objective:To identify the pathogenic mutation in a five-generation Ningxia family with autosomal dominant retinitis pigmentsoa (adRP) and to analyze its associated clinical phenotype.Methods:One adRP pedigree was recruited for this study.All the patients and family members received complete ophthalmic examinations.DNA was abstracted from peripheral blood of three patients, one normal family member and 300 normal controls.Using whole exome sequencing (WES) chip and bioinformatics analysis to screen the candidate disease-causing mutations.PCR and direct sequencing were used to confirm the disease-causing mutations.Genotype-phenotype correlation was also analyzed.This study followed the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of People's Hospital of Ningxia Hui Autonomous Region (No.20160204).Results:PRPF31 c. C1048T (p.Q350X) nonsense mutation was identified as the disease-causing mutation for this family by WES chip, PCR and direct sequencing.This family demonstrated early onset of the disease by presenting nyctalopia from 5 to 6 years, performed rapid disease progression, severely impaired visual function and posterior subcapsular cataract.The fundus presentations and electroretinogram (ERG) results showed typical RP progressions. Conclusions:PRPF31 c. C1048T (p.Q350X) nonsense mutation is the disease-causing mutation of this family.This mutation is first reported in Chinese with distinct phenotypes in the present family, including early onset of the disease, rapid disease progression, severely impaired visual function and posterior subcapsular cataract.

Objective: To analysis the gene mutation spectrum of retinitis pigmentosa (RP) patients in Ningxia Region of China. Methods: Fifty-five pedigrees and 74 sporadic RP patients were included in Ningxia Eye Hospital from January 2015 to December 2016.Two hundred unrelated healthy adults were enrolled as normal controls during the same period.The clinical features of patients and their family members were evaluated by ophthalmic examinations, including visual acuity, best corrected visual acuity, fundus examination, optical coherence tomography, fundus fluorescein angiography, and visual field and electroretinogram.The next generation sequencing, PCR and direct sequencing were used to confirm the pathogenic mutation.This study was approved by Ethic Committee of the Ningxia Eye Hospital (NO.20150107), and informed consent was obtained from each subject. Results: The mutations were detected in 37 RP pedigrees, 8 pedigrees showed autosomal dominant inheritance and 6 pathogenic genes were confirmed, all the autosomal dominant RP (ADRP) patients carried a single heterozygous mutation.Twenty-five pedigrees were autosomal recessive RP (ARRP) and 12 pathogenic genes were confirmed.Among ARRP patients, the mutations rate of USH2A gene was the highest, accounting for 28% (7/25), EYS gene and MYO7A gene accounted for 12% (3/25). Four X-linked RP (XLRP) pedigrees carried the homozygous mutations on RPGR gene.Twenty-five disease-causing genes were detected in 49 sporadic RP patients.The mutation rate of USH2A gene was the highest, accounting for 26.5% (13/49), followed by RP1 gene, accounting for 8.1% (4/49). Conclusions Recessive inheritance is the most common cause of RP.USH2A gene is the main pathogenic gene of RP in Ningxia region of China.

Objective To analyze the relationship between genotype and phenotype in 3 pedigrees with Stargardt disease.Methods Three pedigrees with Stargardt disease were included in Ningxia Eye Hospital from January 2017 to September 2017.The clinical features of patients and other family members were evaluated by ophthalmic examinations,including visual acuity,best corrected visual acuity (BCVA),fundus examination,optical coherence tomography (OCT),fundus fluorescein angiography (FFA) and electroretinogram (ERG).The periphery blood sample of 5 ml from patients and 1 family member with normal phonotye in each family were collected.The next generation sequencing,PCR and direct sequencing were used to confirm the disease-causing mutation.The relationship between genotype and phenotype was analyzed.This study was approved by Ethic Committee of Ningxia Eye Hospital and informed consent was obtained from each subject.Results In 3 Stargardt pedigrees,2 pedigrees showed autosomal recessive inheritance,and 1 pedigree was pseudodominant inheritance.Five mutations on ABCA4 gene were detected and p.F2188S and p.Y345C were novel muations.All pedigrees carried two heterozygous mutation.The onset age of the patients were adolescence except just one patient who suffered at the age of 50 years old.The visual acuity was severely affected and the OCT indicated different degrees of macular atrophy.The results of the ocular fundus photography and the FFA were variable.Conclusions The patients with stargardt disease often carry heterozygous mutation on ABCA4 gene and available characteristics,including early onset age,varying ocular fundus and severe visual impairment.Next generation sequencing technique shows the advantages of rapid and high efficiency in the diagnosis of Stargardt disease.

Objective To observe the effects of transcutaneous electrical acupoint stimulation (TEAS) on hand dysfunction after stroke. Methods From March, 2013 to June, 2015, 56 cases of stroke with hand dysfunction were divided into group A (n=28) and group B (n=28). Both groups received basic rehabilitation, while group B received TEAS in addition, for six weeks. They were evaluated with Brunnstrom Grades, Manunl Muscle Test (MMT), Fugl- Meyer Assessment (FMA) of fingers, Motor Status Scale (MSS), modified Ashworth Scale (MAS), National Institutes of Health Stroke Scale (NIHSS), Motor Hand Functional Status Score and Barthel Index (BI). Results The scores of FMA of fingers, MMT of wrist flexion, MSS, MAS and BI were more in group B than in group A (t>2.2527, P<0.05), and the score of NI-HSS was less in group B (t=3.556, P<0.001). There was no significant difference between two groups in the score of Motor Hand Functional Status Score and MMT of wrist extension (t<0.310, P>0.05). Conclusion TEAS can promote the recovery of hand function and the activi-ties of daily living in patients after stroke.