OBJECTIVE: We investigated the safety and efficacy of haploidentical stem cell transplantation (SCT) in pediatric patients with X-linked adrenoleukodystrophy (ALD). METHODS: A retrospective analysis of transplantation data from 29 cases of ALD, treated between December 2014 and April 2022, was conducted. Neurologic function scores (NFS) were assessed. The conditioning regimen was busulfan 9.6 mg/kg, cyclophosphamide 200 mg/kg, and fludarabine 90 mg/m2 (BFC). Graft-versus-host disease prophylaxis consisted of anti-human thymocyte globulin, cyclosporine A, mycophenolate mofetil, and short course of methotrexate. RESULTS: Among the 29 cases, 14 cases (NFS = 0) were asymptomatic, and 15 (NFS ≥ 1) were symptomatic. The median age at SCT was 8 years (range: 4-16 years); the median follow-up time was 1058 days (range: 398-3092 days); 28 cases were father donors and 1 case was a grandfather donor. Hematopoietic reconstitution was successful in all patients, and all of them achieved complete donor chimerism at the time of engraftment. The leading cause of death was still primary disease progression (n = 4). Survival free of major functional disabilities was 100% in asymptomatic patients versus 66.67% in the symptomatic group (p = .018). CONCLUSION: BFC regimen used in haploidentical SCT was administered safely without major transplant-related complications even in symptomatic patients, and neurological symptoms were stabilized after SCT.
Adrenoleukodystrophy , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Vidarabine/analogs & derivatives , Humans , Child , Child, Preschool , Adolescent , Busulfan/therapeutic use , Retrospective Studies , Graft vs Host Disease/etiology , Transplantation Conditioning/adverse effects , Hematopoietic Stem Cell Transplantation/adverse effects , Cyclophosphamide/therapeutic use , Antilymphocyte Serum/therapeutic use , Adrenoleukodystrophy/therapy , Adrenoleukodystrophy/complications
OBJECTIVES: We investigated the clinical outcome of stenting of unprotected left main coronary artery (LMCA). METHODS: We studied 164 patients with nonbifurcated LMCA lesions (group A) and 96 patients with distal bifurcated lesions (group B). RESULTS: Clinical follow-up was available in 100%. Angiographic follow-up was 87.3% in group A and 86% in group B (p = 0.922). There were significant differences in major adverse cardiac events at 1 (p = 0.014) and 2 years (p = 0.002) between group B (19.8%, 25.0%) and group A (9.1%, 10.4%), mainly due to increased target-vessel revascularization (16.7, 21.9% in group B vs. 6.1, 7.3% in group A, p = 0.006 and 0.001, respectively). The double-stent technique was associated with worse outcomes at 1 year in group B compared to group A. Bifurcation lesions (HR 3.42, 95% CI 1.34-5.61, p = 0.001), diabetes (HR 2.68, 95% CI 2.01-12.11, p = 0.015), three-vessel disease (HR 0.83, 95% CI 0.27-0.96, p = 0.001), incomplete revascularization (HR 0.15, 95% CI 0.11-0.35, p = 0.001) and stent diameter (HR 5.05, 95% CI 2.71-10.01, p = 0.03) were the independent factors of major adverse cardiac events in the whole patient cohort. CONCLUSION: Stenting unprotected distal bifurcated LMCA was associated with unfavorable results when compared to stenting other LMCA lesions.
Angioplasty, Balloon, Coronary/adverse effects , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Drug-Eluting Stents/adverse effects , Aged , Coronary Artery Disease/epidemiology , Disease-Free Survival , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Predictive Value of Tests , Prevalence , Proportional Hazards Models , Registries , Risk Factors , Stroke Volume , Treatment Failure , Treatment Outcome
OBJECTIVE: To analyze the mutation of Leber's hereditary optic neuropathy (LHON) and the clinical features in Chinese patients. METHODS: The primary mtDNA mutations (3460A, 11778A and 14484C) of 156 patients (110 probands and 46 maternal relatives with LHON) were detected by mutation-specific priming polymerase chain reaction, heteroduplex-single strand conformation polymorphism polymerase chain reaction, restriction fragment length polymorphisms and measurement of DNA sequence. The clinical features were analyzed by retrospective study. RESULTS: The 11778A mutation was found in 100 probands (90.9%), the 3460A mutation was found in 2 (1.8%), and the 14484C was found in 8 (7.3%) of the 110 probands. The visual acuity at onset of the disease was 0.01 or worse in 44 (17.6%) of 250 eyes with the 11778A mutation, but in none of 79 eyes with the 14484C mutation. The visual acuity was 0.1 or better in 76 (29.6%) of 250 eyes with the 11778A mutation, but in 49 (87.3%) of 56 eyes with the 14484C mutation. And 6.8% of 250 eyes with the 11778A mutation recovered a mean final visual acuity of 0.03, whereas 50% of 56 eyes with the 14484C mutation recovered a mean final visual acuity of 0.8. CONCLUSION: In Chinese LHON patients the 11778A, 14484C primary mutations are common. The clinical features are associated with the site of primary mutation. The visual acuity at onset of the disease and the visual recovery of the eyes with 14484C mutation were better than the eyes with the 11778A mutation.
Mutation , Optic Atrophy, Hereditary, Leber/genetics , Optic Atrophy, Hereditary, Leber/pathology , Adolescent , Adult , Asian People/genetics , Child , China , DNA Mutational Analysis , DNA, Mitochondrial/chemistry , DNA, Mitochondrial/genetics , Female , Gene Frequency , Humans , Male , Optic Atrophy, Hereditary, Leber/ethnology , Polymerase Chain Reaction , Young Adult
Glaucoma is one of the leading causes of irreversible blindness. The genetic changes play an important role in the pathogenesis of glaucoma. Progress in human genome project (HGP) and the application of molecular genetics in the study of glaucoma has leaded to an important progress in the understanding of etiology of glaucoma. It is still difficult to predict the influence of these progresses on the early diagnosis, prevention and treatment of glaucoma. However, this may provide a series of problem that require exploration and shows the changing direction of glaucoma study in the future.
Glaucoma/genetics , Humans
<p><b>OBJECTIVE</b>To analyze the mutation of Leber's hereditary optic neuropathy (LHON) and the clinical features in Chinese patients.</p><p><b>METHODS</b>The primary mtDNA mutations (3460A, 11778A and 14484C) of 156 patients (110 probands and 46 maternal relatives with LHON) were detected by mutation-specific priming polymerase chain reaction, heteroduplex-single strand conformation polymorphism polymerase chain reaction, restriction fragment length polymorphisms and measurement of DNA sequence. The clinical features were analyzed by retrospective study.</p><p><b>RESULTS</b>The 11778A mutation was found in 100 probands (90.9%), the 3460A mutation was found in 2 (1.8%), and the 14484C was found in 8 (7.3%) of the 110 probands. The visual acuity at onset of the disease was 0.01 or worse in 44 (17.6%) of 250 eyes with the 11778A mutation, but in none of 79 eyes with the 14484C mutation. The visual acuity was 0.1 or better in 76 (29.6%) of 250 eyes with the 11778A mutation, but in 49 (87.3%) of 56 eyes with the 14484C mutation. And 6.8% of 250 eyes with the 11778A mutation recovered a mean final visual acuity of 0.03, whereas 50% of 56 eyes with the 14484C mutation recovered a mean final visual acuity of 0.8.</p><p><b>CONCLUSION</b>In Chinese LHON patients the 11778A, 14484C primary mutations are common. The clinical features are associated with the site of primary mutation. The visual acuity at onset of the disease and the visual recovery of the eyes with 14484C mutation were better than the eyes with the 11778A mutation.</p>
Adolescent , Adult , Child , Female , Humans , Male , Young Adult , Asian People , Genetics , China , DNA Mutational Analysis , DNA, Mitochondrial , Chemistry , Genetics , Gene Frequency , Mutation , Optic Atrophy, Hereditary, Leber , Ethnology , Genetics , Pathology , Polymerase Chain Reaction
To investigate the association between variations of ZFP161 gene and high myopia, A total of 204 probands with simple high myopia(< or = -6.0 dipoters) were collected while 116 normal persons from different families without high myopia or related disease were used as controls. Genomic DNA was prepared from the peripheral leucocytes. The coding sequences of ZFP161 gene in 320 subjects were analyzed by using exon-by-exon PCR-heteroduplex-SSCP analysis. Identification of the Variations by cloning and sequencing, combinated with controls and family analysis, was used to disclose the correlation between ZFP161 gene and high myopia. A mutation of ZFP161 gene was identified as an insertion of AT before the 58th nucleotide of intron 1 (IVS1 58-59)(1/204) and a variation of ZFP161 gene was identified as a heterozygous C to A of the 168th nucleotide in exon 2 (Codon56, GCC-->GCA, Ala56Ala). Ala56Ala is a non-sense mutation identified in 5 of the 204 patients and 3 of 116 controls. No evidence shows that these variations are responsible for high myopia.
Asian People/genetics , DNA-Binding Proteins/genetics , Exons/genetics , Mutation , Myopia/genetics , Repressor Proteins/genetics , Base Sequence , China , Codon, Nonsense , DNA/genetics , Humans , Introns/genetics , Kruppel-Like Transcription Factors , Mutagenesis, Insertional , Myopia/metabolism , Point Mutation , Polymerase Chain Reaction , Polymorphism, Single-Stranded Conformational
OBJECTIVE: To screen the variations of TG interacting factor(TGIF) gene in encoding sequence in Chinese high myopia patients and normal controls and to analyze the SNPs of TGIF gene encoding sequence in Chinese population. METHODS: Genomic DNA was collected from 204 probands with high myopia and 112 unrelated persons without high myopia. The coding sequences of TGIF gene in 316 subjects were analyzed by using exon-by-exon PCR heteroduplex-SSCP analysis and sequencing. RESULTS: There were 3 types of SNP and one single nucleotide mutation in the coding sequence of TGIF gene: IVS-2 nt350 G --> T(36/204), codon140 CCA --> CCG; Pro140Pro codon163 CCG --> CTG;Pro163Leu and codon126 GTG --> GCG; Val126Ala(1/204). The SNPs of codon140 CCA --> CCG and codon163 CCG --> CTG were composed of 3 alleles and 5 genotypes in Chinese population which abide by Hardy-Weinberg law. CONCLUSION: There was no evidence to prove that mutations in the TGIF gene are responsible for the high myopia in Chinese. Three SNPs of coding sequence TGIF gene in Chinese population abide by Hardy-Weinberg law.
Homeodomain Proteins/genetics , Myopia/genetics , Polymorphism, Single Nucleotide , Repressor Proteins/genetics , China , DNA/chemistry , DNA/genetics , DNA Mutational Analysis , Gene Frequency , Humans , Mutation , Myopia/pathology , Polymerase Chain Reaction , Polymorphism, Single-Stranded Conformational
<p><b>OBJECTIVE</b>To screen the variations of TG interacting factor(TGIF) gene in encoding sequence in Chinese high myopia patients and normal controls and to analyze the SNPs of TGIF gene encoding sequence in Chinese population.</p><p><b>METHODS</b>Genomic DNA was collected from 204 probands with high myopia and 112 unrelated persons without high myopia. The coding sequences of TGIF gene in 316 subjects were analyzed by using exon-by-exon PCR heteroduplex-SSCP analysis and sequencing.</p><p><b>RESULTS</b>There were 3 types of SNP and one single nucleotide mutation in the coding sequence of TGIF gene: IVS-2 nt350 G --> T(36/204), codon140 CCA --> CCG; Pro140Pro codon163 CCG --> CTG;Pro163Leu and codon126 GTG --> GCG; Val126Ala(1/204). The SNPs of codon140 CCA --> CCG and codon163 CCG --> CTG were composed of 3 alleles and 5 genotypes in Chinese population which abide by Hardy-Weinberg law.</p><p><b>CONCLUSION</b>There was no evidence to prove that mutations in the TGIF gene are responsible for the high myopia in Chinese. Three SNPs of coding sequence TGIF gene in Chinese population abide by Hardy-Weinberg law.</p>
Humans , China , DNA , Chemistry , Genetics , DNA Mutational Analysis , Gene Frequency , Homeodomain Proteins , Genetics , Mutation , Myopia , Genetics , Pathology , Polymerase Chain Reaction , Polymorphism, Single Nucleotide , Polymorphism, Single-Stranded Conformational , Repressor Proteins , Genetics
To screen possible disease-causing mutations in the GUCA1B gene, GNGT1 gene,and the alternative-splicing region of RGS9 gene in 120 probands with retinitis pigmentosa,genomic DNA was collected from 120 probands with retinitis pigmentosa out of 120 families. The coding sequences of the GUCA1B and GNGT1 genes and the alternative splicing region of the RGS9 gene were analyzed by using PCR-heteroduplex-SSCP method. Mutation was confirmed by DNA sequencing. A T/C polymorphism was identified in exon 1 of the GUCA1B gene in 31 of the 120 probands. Heteroduplex-SSCP analysis of the GUCA1B and GNGT1 coding regions and RGS9 alternative splicing region showed no mutations in 120 patients with retinitis pigmentosa. We found no evidence that mutation in GUCA1B,GNGT1,or RGS9 gene is a cause of retinitis pigmentosa.
To analyze the relationship of the peripherin gene(PRPH, OMIM17071) mutations with high myopia,genomic DNA was collected from 180 probands with high myopia (
