Phenotype/genotype analysis of 4 cases of LMNA related congenital muscular dystrophy with inflammatory changes / 中华实用儿科临床杂志

Objective To analyze the clinical characteristics,muscle pathological features and pathogenic gene mutation in 4 cases with LMNA-related congenital muscular dystrophy (L-CMD).Methods Clinical data of the probands and the parents were collected.Skeletal muscle specimens were biopsied from the probands for pathological analysis.Genomic DNA and RNA were extracted from peripheral blood leukocytes,and PCR,reverse transcription(RT)-PCR and DNA direct sequencing were employed to analyze the LMNA gene to determine the gene mutation and confirm the pathogenicity.Results Four patients had symptoms from fetal period to several months after birth.They presented with motor retardation,muscle weakness with prominent the proximal upper limbs,distal lower limbs and neck extensor,hypotonia,contractures,with mild to moderate elevation of CK level.The muscle biopsies showed muscular dystrophic and with inflammatory changes,and the abnormal nuclear morphology was observed with transmission electron microscopy.Genetic analysis of them detected 4 dominant de novo mutations.Three of them had unreported pathogenic mutations.The same sites of the LMNA gene were wild type in their parents.Conclusions Four cases of L-CMD are genetically identified.Genetic counseling of the family can be possible.The patients should be considered LMNA gene mutation of they present themselves with muscle weakness with the proximal upper limbs,distal lower limbs and neck extensor,hypotonia,contractures,mild to moderate elevation of CK level,and if the biopsies show muscular dystrophic changes but also with inflammatory changes should be considered LMNA gene mutation.Genetic analysis is the most reliable method for diagnosing L-CMD.

Genetic analysis and prenatal diagnosis for a family with megalencephalic leukoencephalopathy and subcortical cysts / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify potential mutation in the MLC1 gene in a Chinese family affected with megalencephalic leukoencephalopathy and subcortical cysts (MLC), and to provide prenatal diagnosis.</p><p><b>METHODS</b>Genomic DNA of the patients, their parents and younger sister were extracted from peripheral blood. That of the fetus was extracted from an amniotic fluid sample. A total of 12 exons and at least 100 bp flanking the intronic sequence of the MLC1 gene were amplified with PCR. MLC1 mutations were screened by sequencing. Linkage analysis was performed for the family to assure accuracy of prenatal diagnosis.</p><p><b>RESULTS</b>The two patients were both heterozygote for c.177_178delG (p.Ser60AlafsX5) mutation in exon 2 and c.598-2A>C change in intron 7. The c.177_178delG mutation was inherited from the father, and the c.598-2A>C mutation was inherited from the mother. The younger sister and the fetus have both inherited c.177_178delG from the father but did not inherit c.598-2A>C from the mother. Prenatal diagnosis suggested the fetus to be a carrier for a MLC1 mutation. Linkage analysis was consistent with the result of mutation detection. The fetus was born normal as predicted.</p><p><b>CONCLUSION</b>The c.598-2A>C is a novel splicing mutation. Prenatal diagnosis through DNA sequencing and linkage analysis were performed for the first time on Chinese patients with MLC.</p>

Preliminary Observation of Ketogenic Diet Therapy for Children with Intractable Epilepsy / 实用儿科临床杂志

Objective To observe the therapeutic effect of ketogenic diet therapy for children with intractable epilepsy and its safety.Methods Fifteen patients with intractable epilepsy were treated with ketogenic diet that was modified specifically for Chinese people.The compliance,seizure frequency and side effects were followed up.Results Twelve patients maintained on the treatment for 1 month.Among them,the reduction of seizure frequency in 10 patients exceed 50%.Ten patients maintained on the treatment for 3 months.Among them,the reduction of seizure frequency in 8 patients exceed 50%.Five patients maintained on the treatment for more than 6 months.The reduction of seizure frequency all exceed 50%.The reduction of seizure frequency in 4 patients exceed 90%.The seizures of 3 patients were controlled completely.Ten patients among all cases had various adverse effect,such as nausea,vomiting,diarrhea,constipation,hypoglycemia(nonsymptomatic),hyperlipemia and damage of liver function and so on,which could eliminate by anti-symptomatic treatment.Conclusions Ketogenic diet is effective and safe in Chinese children with intractable epilepsy with modified methods specifically for Chinese.The effect is unrelated with seizure types obviously.