The Clinical Study and HLA Genotyping of 112 Familial Myasthenia Gravis Patients

Summary: One hundred and twelve cases of familial myasthenia gravis (MG) from 44 families selected from 2100 patients with MG diagnosed since 1983 in the Department of Neurology were studied. The clinical pictures and immunological features of the patients showed a great resemblance to those of sporadic cases. The pedigree analysis disclosed that the hereditary patterns of familial patients were basically Mendellian autosomal inheritance. Many predisposing factors such as fever, infection, use of aminoglycoside or vaccines, played an important role in presenting the phenotype of subclinical cases. The HLA genotyping suggested that the complement polymorphism C4A*4, the complotype S42, and the genes 0901 and 1301 of DRB1 allele, were related to the pathogenesis of MG. It was concluded that the phenotype of MG may be the result of interaction between hereditary defects and environmental factors.

The Gene of Megalencephalic Leukoencephalopathy with Subcortical Cysts is Mapped on Chromosome 22q13.3 with 250 kb Interval

Objective: Vacuolating megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a recently described syndrome with autosomal recessive mode of inheritance. Its possible gene was located on chromosomal 22q tel with 3-cM. The purpose of this study was to narrow down the genetical distance on chromosomal 22q tel with MLC. Methods: Thirty-nine MLC patients in 33 families were collected,and the linkage analysis and haplotype analysis of twelve informative families were done, using seven microsatellite markers and four SNP markers. Results: The maximum tow-point LOD score for marker 355c18 was 6.65 at recombination fraction 0.02. The haplotype analysis narrowed down the critical region of MLC to 250 kb on chromosomal 22q tel. Conclusion: One of the causing genes of MLC was located on chromosomal 22q tel with 250 kb. Four candidate genes were considered. The heterogeneity of one informative family indicated possible existence of a second locus for MLC.

Megalencephalic Leukoencephalopathy with Subcortical Cysts-a New Child Leukoencephalopathy

Here we review a new variety of leukoencephalopathy with infantile megalencephaly and discrepant clinical course (MLC, MIM: 604004). These children had megalencephaly in the first year of life, with or without mild delay of motor function and/or seizures. After a few years, motor handicap was slowly progressive with unsteady gait, serious cerebellar ataxia and mild plasticity. Eventually most of patients were confined to a wheelchair. Meanwhile mental development was relatively preserved, although the learning problems was increased from the midway of elementary school. Most of patients had tonic-clonic seizure and some might advance to status epilepticus. Antiepileptic drugs may effectively control seizure. The disorders of known metabolic defects were excluded. Neurophysiological examination showed that EEG had interictal epileptic discharges on the generalized slow wave background in most patients. The cerebral white matter had diffuse abnormality, with swelling of white matter, and cysts in the frontoparietal and anterior-temporal lobes on MRI examination. Some central white matter structures were spared, such as corpus callosum. The severity of lesions on MRI is inconsistent with the clinical signs. Pathogenesis of this disease was unknown. The pathological findings found a spongiform leukoencephalopathy due to myelin splitting and intramyelinic vacuole formation but without myelin loss. This disease had probably an autosomal recessive inheritance. The gene KIAA027 on 22qtel was responsible for MLC.

Autosomal dominant coralliform cataract related to a missense mutation of the γD-crystallin gene

Background Congenital cataract is a sight-threatening disease that affects about 1-6 cases per 10000 live births and causes 10%-30% of all blindness in children About 25% of all cases are due to genetic defects We identified autosomal dominant congenital coralliform cataracts-related genetic defect in a four-generation Chinese family Methods Complete ophthalmological examinations were performed prior to lens extraction Lens samples were then studied by electron microscopy Genomic DNA from family members were examined using whole-genomic linkage analysis, with two-point logarithm of odds (LOD) scores calculated using the Linkage program package (version 5 1) Mutation analysis of candidate genes was performed by direct sequencing Finally, a three-dimensional protein model was predicted using Swiss-Model (version 2 0) Results Eleven of the 23 examined individuals had congenital cataracts Ultrastructure studies revealed crystal deposits in the lens, and granules extensively dispersed in transformed lens fiber cells The maximum two-point LOD score, 3 5 at θ=0 1, was obtained for the marker D2S325 Mutation analysis of the γ-crystallin (CRYG) gene cluster identified a mutation (P23T) in exon 2 of γD-crystallin (CRYGD) Protein structure modeling demonstrated that the P23T mutation caused a subtle change on the surface of the γD protein Conclusions The results suggest that the coralliform cataract phenotype is due to a mutated CRYGD gene, and that this sequence change is identical to one reported by Santhiya to be related to another distinct clinical condition, lamellar cataract This study provides evidence that this same genetic defect may be associated with a different phenotype This is the first report identifying the genetic defect associated with an autosomal dominant congenital coralliform cataract

Decreased osteogenic activity and mineralization of alveolar bone cells from a patient with amelogenesis imperfecta and FAM83H 1261G>T mutation

FAM83H mutations lead to autosomal dominant hypocalcified amelogenesis imperfecta(ADHCAI).However,the biological role of FAM83H remains unclear.The present study aimed to characterize the alveolar bone cells isolated from a patient with ADHCAI having the mutation,c.1261G>T,p.E421*,in FAM83H.We showed that FAM83H mutant cells had proliferation ability and morphology similar to the controls.The F-actin staining revealed that FAM83H mutant cells were remained in the earlier stages of cell spreading compared to the controls at 30 min,but their spreading was advanced comparable to the controls at later stages.After osteogenic induction,a significant decrease in mRNA levels of RUNX2 and ALP was observed in FAM83H mutant cells at day 7 compared with day 3 while their expressions were increased in the controls.The OPN levels in FAM83H mutant cells were not significantly changed at day 7 compared to day 3 while the controls showed a significant increase.After 14 days,the mineral deposition of FAM83H mutant cells was slightly lower than that of the controls.In conclusion,we identify that FAM83H bone cells have lower expression of osteogenic marker genes and mineralization while they maintain their morphology,proliferation,and spreading.Consistent with previous studies in the ameloblasts and periodontal ligamental cells,these evidences propose that FAM83H influences osteogenic differentiation across different cell types in oral cavity.