A case of Cockayne syndrome caused by ERCC8 gene mutation / 临床儿科杂志

Objective To explore the clinical,radiological and gene mutation features ofERCC8 gene in one patient with Cockayne syndrome.Methods Clinical and radiological data of a girl diagnosed with Cockayne syndrome through gene detection were retrospectively analyzed.Next-generation sequencing was used to detect genetic cause.Sanger sequencing was used to confirm the candidate variants and detect mutations in her parents and sister.ResuRs The patient showed psychomotor retardation,growth failure,special face,and light sensitivity.Neurological examination revealed noticeable developmental delay,motor impairment,spastic paralysis,and cerebellar ataxia.Brain MRI revealed symmetrical demyelination of bilateral centrum semiovale and periventricular white matter.The cerebellum was atrophic.The patient was found to have compound heterozygous mutations of c.397C＞T(p.Q133X) and c.394_398del(p.L132fs).Sanger sequencing showed these two mutations were inherited from her mother and father respectively.Conclusions Next-generation sequencing technology is a useful tool for the detection of mutation in ERCC8 gene,which is valuable for the diagnosis of Cockayne syndrome.These two mutations expanded the mutation spectrum of Cockayne syndrome in Chinese population.

Biotinase deficiency manifested as encephalomyelopathy: a case report and literature review / 临床儿科杂志

Objective To explore the diagnosis and treatment of biotinase deficiency (BTD) manifested as encephalomyelopathy.Methods The clinical data of one child with BTD were retrospectively analyzed.The pertinent literatures were reviewed.Results A six-year-old male child suffered from progressive spastic paralysis of lower limbs for 3 months before admission.A similar symptoms occurred after a cold in 3-year-old.It was easy to peel skin on her hands and she had angular stomatitis.Audio visual evoked potential was detected to be abnormal in other hospital.After hospitalizion,the cerebrospinal fluid examination was normal,and MRI showed long T1 long T2 signals bilateral occipital lobe and basal ganglia region.Because the child represented medulla palsy,and so the tracheal intubation ventilator was administrated to assist ventilation.Urine gas chromatography/mass spectrometry (GC/MS) analysis showed increases of lactic acid,3-hydroxy acid,3-tiglyl glycine,methylcitric acid,and ethylene lactic acid.Serum MS/MS analysis showed that the concentrations of propionyl camitine and 3-hydroxyisovaleryl carnitine were increase obviously.The serum biotinase level was significantly decrease to 0.076 pmol/(min·mm3).The diagnosis of BTD was confirmed.After supplementation biotin,40 mg/d,the ventilator was successfully weaned on the third day,the child walked again after 2 weeks,and the rash was vanished.After 3 weeks,the head MRI showed disappearance of the original lesion,and there was no abnormal in spinal cord.The BTD gene detected by PCR direct sequencing showed a heterozygosis mutation of T172T/C in the second exon and a homozygous mutation of T1413C in the fourth exon,which was confirmed as a pathogenic mutation by pedigree verification and database query.After discharge,the oral administration of biotin 20 mg/d continued,and no abnormality was found in 2 years of follow-up.Conclusions The manifestations of BTD are complex and diverse.The analysis of urine GC/MS and serum MS/MS can assist the diagnosis.The determination of biotinase activity and gene detection of BTD can further confirm the diagnosis.Timely biotin supplementation has significant treatment efficacy.

Application of next generation sequencing technology for genetic diagnosis of a case with globoid cell leukodystrophy / 临床儿科杂志

Objective To explore the clinical, radiological features and gene mutation of GALC gene in one child with globoid cell leukodystrophy (Krabbe disease). Methods The clinical and radiological data of a patient diagnosed with Krabbe disease through next-generation sequencing were retrospectively analyzed. Sanger sequencing was used to confirm the results. Results The patient was late infantile form with main manifestations of progressive psychomotor regression and convulsion. Brain MRI showed symmetric long T1 and long T2 signal changes in the white matter next to lateral ventricle angle, posterior limb of internal capsule, and the ministry of corpus callosum. The patient was found to have compound heterozygous mutations of c.1832T>C in exon 15 and c.979T>G in exon 9, which resulted in amino acid changes of p.L611S and p.F327V, respectively. Sanger sequencing results showed that the two heterozygous mutations were correspondingly inherited from his mother and father. Conclusions Next-generation sequencing technology is a useful tool for the detection of GALC gene mutation, which is valuable for definite diagnosis and differential diagnosis of Krabbe disease in clinical practice.

The applications of video-electroencephalogram in the pediatric intensive care unit and the neonatal intensive care unit / 中国小儿急救医学

Cerebral injury is a common disease in the pediatric intensine care unit(PICU)and the neonatal intensive care unit (NICU).Video-electroencephalogram examination can help for the etidogical diagnosis,illness monitoring and prognosis assessment.The article is a review about the applications of video-electroencephalogram in common diseases in NICU and PICU.

Microarray detection of the copy number variations in a patient with developmental delay / 临床儿科杂志

Objective To investigate the copy number variants of a developmental delay patient by applying single nucleotide polymorphisms array technique and to analyze the relationship between the clinical manifestation and copy number variants.Methods Single nucleotide polymorphisms array was used to detect genomic copy number variants in a child with development delay and her phenotypic normal parents.Results The patient had a 7. 9-Mb deletion at 8p23.3-p23.1 and a 27.4-Mb duplication at 8p23.1-p11.23, which were conifrmed as pathogenic copy number variants after comparative analysis with database.Conclusions Single nucleotide polymorphisms array could serve as a useful method to diagnose developmental delay patients and analyze pathogenesis.

Clinical-electroencephalogram characteristics and its evolutionary process of Dravet syndrome / 中华神经科杂志

Objective To analyze the clinical and electroencephalogram (EEG) characteristics as well as its evolutionary process of Dravet syndrome (DS) in order to improve early diagnosis and appropriate treatment.Methods Fifty patients with DS were studied including onset age, trigger factors, seizure types on different age stages and relationship with EEG characteristics and its evolution process.Results The average age of seizure onset was ( 5.5 ± 1.9 ) months.The fever sensitivity continuously existed in the entire course of disease.In the early stage, generalized tonic-clonic seizures (GTCS) and focal or unilateral seizures were main types.Multi seizure types included myoclonic seizures (MS) and atypical absence occurred later.The onset ages of MS were average (M50) of 16 months.MS never occurred in 26% of the patients.During the first year of life, EEGs were normal in 76% of these patients.The epileptiform discharges only recorded in about 50% of the patients in spite of multi seizure types had presented.After three years ago, both EEG background abnormalities and discharges occurred in more 90% of the all patients.Photosensitivity response with MS occurred in the 28% of 18 patients.Conclusions The clinical and EEG are not parallel progressively process in early stage of DS.The children often express more severe clinical seizures than EEG abnormalities until 2 years of age.Various abnormal EEG manifestation obviously display gradually after 3 years age.Precise recognizing with the clinical and EEG characteristics of DS will help get correct early diagnosis and screen the candidate cases to test SCN1A gene.

Mutation analysis of the SCN1A gene in severe myoclonic epilepsy of infancy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the mutations of the sodium channel alpha 1 subunit gene SCN1A in severe myoclonic epilepsy of infancy (SMEI) patients and analyze its inheritance.</p><p><b>METHODS</b>Twenty-three patients consistent with the diagnosis of SMEI were selected for SCN1A mutation analysis. Genomic DNA was extracted from peripheral blood lymphocytes of these patients and their parents. All the twenty-six exons of the SCN1A gene were amplified by PCR and sequenced.</p><p><b>RESULTS</b>In the 23 SMEI patients, 17 mutations were identified in 17 unrelated SMEI patients. The SCN1A mutation rate was 73.9% (17/23). The mutations included 8 missense mutations (F90S, I91T, A239T, W952G, T1210K, V1335M, V1390M and G1433E), 3 nonsense mutations (R612X, W768X and W1408X), 3 deletion mutations (A395fsX400, L556fsX557 and V1778fsX1800), 1 insertion mutation (Y1241fsX1270), 1 splice-site mutation (IVS10+3 A to G) and 1 synonymous mutation (K1492K), of which 47.1% (8/17) were truncation mutations. Thirteen mutations (F90S, I91T, T1210K, V1335M, G1433E, R612X, W768X, A395fsX400, L556fsX557, V1778fsX1800, Y1241fsX1270, IVS10+3A to G and K1492K) have not been reported previously. Except for F90S, L556fsX557 and V1778fsX1800, the other 14 mutations were de novo.</p><p><b>CONCLUSION</b>SCN1A is a major pathogenic gene for SMEI. About a half of the SCN1A mutations in SMEI cause truncation. There were no hotspots of SCN1A mutations in SMEI patients, and most mutations were de novo.</p>

Analysis of the GABRG2 gene mutation in a Chinese family with generalized epilepsy with febrile seizures plus / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify the mutation of the GABA(A)-receptor gamma 2 subunit gene (GABRG2) in a Chinese family with generalized epilepsy with febrile seizures plus (GEFS+ ) and analyze the genotype-phenotype correlations and its inheritance.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood lymphocytes of the proband and other available members in the GEFS+ family. The coding regions and flanking intronic regions of the GABRG2 gene were screened for mutations using polymerase chain reaction (PCR) and direct DNA sequencing.</p><p><b>RESULTS</b>There were 7 affected members in the three-generation family, in which one with febrile seizures (FS) and six with febrile seizures plus (FS+ ). This family was consistent with the diagnostic criteria of GEFS+ . The nonsense mutation c.1287G to A (p.W390X) in the GABRG2 gene was initially identified in the proband. Seven affected members (6 FS+ and 1 FS) and one unaffected member carried the mutation. The nonsense mutation c.1287G to A/p.W390X in the GABRG2 gene was co-segregated with the GEFS+ family. The penetrance rate was about 87.5%(7/8).</p><p><b>CONCLUSION</b>This GEFS+ family was consistent with autosomal dominant inheritance with incomplete penetrance. GABRG2 mutation is also a disease-causing mutation in Chinese GEFS+ patients. The p.W390X mutation has not been reported previously.</p>