ABSTRACT
The clinical data of a patient with megalencephalic leukoencephalopathy (MLC) with subcortical cysts and her parents were collected. MLC1 gene mutation was detected by polymerase chain reaction and direct DNA sequencing. The patient presented with motor developmental delay and giant skull, and brain magnetic resonance imaging showed diffuse white matter swelling accompanied by subcortical cysts in bilateral frontal and parietal lobes. Gene sequencing identified two heterozygous mutations of MLC1, including missense mutation in exon 3 (c.217G>A, p.Gly73Arg) and splice site mutation in intron 9 (c.772-1G>C in IVS9-1). The patient's parents both had heterozygous mutation c.772-1G>C in IVS9-1 with normal phenotype. It can be presumed that c.772-1G>C in IVS9-1 comes from the parents, and c.217G>A (p.Gly73Arg) is a de novo mutation.
Subject(s)
Female , Humans , Infant , Asian People , Genetics , Cysts , Genetics , Hereditary Central Nervous System Demyelinating Diseases , Genetics , Membrane Proteins , Genetics , MutationABSTRACT
<p><b>OBJECTIVE</b>To detect subtelomeric copy number variations in children with genetic intellectual disability (ID) using multiplex ligation-dependent probe amplification (MLPA), and to investigate the pathogenesis of genetic ID.</p><p><b>METHODS</b>A total of 68 children with ID who had normal results of G-banding karyotype analysis were included in the study. Their subtelomeric copy number variations were detected using MLPA P036.</p><p><b>RESULTS</b>Among the 68 children with ID, 7(10%) showed subtelomeric copy number variations, and all the variations were deletion mutations. Among them, 1 case carried 2 subtelomeric microdeletions, and 1 case carried 4 subtelomeric microdeletions.</p><p><b>CONCLUSIONS</b>Subtelomeric copy number variations are important causes of genetic ID. MLPA can be used as an economic and effective method for investigating the pathogenesis of genetic ID.</p>
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , DNA Copy Number Variations , Intellectual Disability , Genetics , Multiplex Polymerase Chain Reaction , TelomereABSTRACT
Objective To explore the influence of antenatal taurine supplementation on the expression of key signaling molecule of Ras homolog gene-Rho associated coiled-coil forming protein kinase-proliferating cell nuclear antigen(Rho-ROCK-PCNAR) pathway in fetal rat brain with intrauterine growth restriction (IUGR),and to understand whether or not taurine can improve neuron regeneration in IUGR fetal rats by this signaling pathway.Methods Thirty pregnant rats were randomly divided into 3 groups:control group,IUGR model(IUGR group) and IUGR + antenatal taufine supplements group(IUGR + taurine group).Taurine was added to the diet of IUGR + taurine group at a dose of 300 mg/(kg · d) from 12 days after conception until natural delivery.The level of mRNA expressions of Ras homolog gene A(RhoA),Rho-associated coiled coil-forming protein kinase 2 gene (ROCK2 gene) and PCNA gene were detected by Real time-PCR.The PCNA positive cell counts were detected by immunohistochemistry.Results 1.The level of RhoA,ROCK2 and PCNA mRNA in the IUGR group,IUGR + taurine group and control group were respectively:RhoA mRNA 1.757±0.041,1.498 ±0.011 and 1.000 ±0.000(P＜0.05);ROCK2 mRNA 1.548 ±0.231,1.094 ±0.049 and 1.000 ± 0.000 (P ＜ 0.05) ; PCNA mRNA 2.007 ± 0.800,3.034 ± 0.670 and 1.000 ± 0.000 (P ＜ 0.05).2.The PCNA positive cell counts in control group,IUGR group and IUGR + taurine group were respectively 11.30 ± 3.18,22.24 ± 6.17 and 77.80 ± 14.60 (P ＜ 0.05).Conclusions Antenatal supplementation of taurine can inhibit the expression of key signaling molecule of Rho-ROCK pathway and improve the expression of PCNA in IUGR fetal brain,which provides a further theoretical basis for the application of antenatal taurine to improve IUGR fetal brain development.
ABSTRACT
<p><b>OBJECTIVE</b>Severe myoclonic epilepsy of infancy (SMEI), or Dravet syndrome, is a severe epileptic encephalopathy. This study aimed to investigate the clinical features and genetic diagnosis of SMEI.</p><p><b>METHODS</b>The electroclinical data and the mutation of SCN1A gene in 13 children with SMEI were analyzed.</p><p><b>RESULTS</b>Of the 13 children, 10 were males and 3 were females. Eight of them had family history of febrile seizures. The average age of seizure onset was 5.6 months, with a range of 2 to 9 months. The initial seizure was a febrile seizure in 9 patients (69%). Generalized or hemiclonic seizures were often triggered by fever. Eight patients had a history of febrile status. Afebrile seizures occurred from 2 months to 21 months of age. All patients went on to develop multiple seizure types. Generalized tonic clonus seizures (GTCS) were found in 11, partial seizures in 12, atypical absence in 10. Myoclonic seizures were presented in all patients. Twelve patients had 3 or more seizure types. Seizures of all patients had a characteristic of temperature sensitivity. The precipitating factors included fever, hot bath and vaccination. Nine patients (69%) had a history of status epilepticus. Delay in mental development was present in 11 cases, ataxia in 5 and pyramidal sign in 2. EEG was normal in most patients in the first year of life, followed by generalized, focal and multifocal discharges. Brain MRI was abnormal in 2 cases. Seizures were not completely controlled in all patients. Carbamazepine and lamotrigine aggravated seizures in some patients. SCN1A gene mutation was found in 10 cases, including seven missense mutations, two nonsense mutations and one frame shift mutation.</p><p><b>CONCLUSION</b>The clinical features of SMEI were seizure onset within one year of age, first event is often a febrile seizure; multiple seizure types and mental delay occurred after the second year of life; seizures have a characteristic of temperature sensitivity; EEG was normal in the first year of life, followed by generalized, focal or multifocal discharges; early diagnosis by testing SCN1A mutation guides selection of antiepileptic drugs.</p>