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Generalized epilepsy with febrile seizures plus (GEFS+) is a childhood genetic epilepsy syndrome. GEFS+ includes a wide spectrum of clinical manifestations, and SCN1A mutations have frequently been reported among the GEFS+-related gene abnormalities. In this study, to clarify the distributions of the clinical subtypes, we analyzed 34 families with GEFS+ in Indonesia using the hospital records of the patients and questionnaires for the family members. The number of patients with febrile seizures plus (FS+), FS+ and afebrile generalized/partial seizures, borderline severe myoclonic epilepsy in infancy (SMEB) and severe myoclonic epilepsy in infancy (SMEI) were 9, 11, 7, and 7, respectively. Most patients had a family history of febrile seizures. Next, we performed molecular analyses to clarify the contributions of SCN1A mutations to the development of the GEFS+ subtypes. Only 3 of 34 probands showed SCN1A mutations. These mutations were two missense mutations, p.V1612I and p.C1756G, in two patients with SMEI and SMEB, and one silent mutation, p.G1762G, in a patient with FS+ and afebrile partial seizures. In conclusion, the majority of GEFS+ patients in Indonesia were not associated with SCN1A mutations. To detect the GEFS+-causing mutations, we must search and analyze other genes in these patients., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Background: Severe myoclonic epilepsy in infancy (SMEI) and borderline SMEI (SMEB) are caused by a mutation in SCN1A, which encodes a voltage-gated sodium channel alpha1-subunit protein. Although many mutations in SCN1A have been associated with clinical features of SMEI or SMEB from different ethnic groups, there have been no such reports from the South-East Asian populations so far., Methods: Patients 1 and 2 were Indonesian children diagnosed as having SMEI and SMEB based on their clinical features. SCN1A was screened for mutations using a combination of polymerase chain reaction and denaturing high-performance liquid chromatography. Nucleotide substitutions were confirmed on direct sequencing., Results: In patient 1, a G-to-A heterozygous transition was detected at nucleotide 4834 (c.4834G>A) in exon 25, leading to substitution of valine with isoleucine at amino acid position 1612 (p.V1612I) in the SCN1A protein. In patient 2 a T-to-G heterozygous transversion was identified at nucleotide 5266 (c.5266T>G) in exon 26, leading to substitution of cysteine with glycine at amino acid 1756 (p.C1756G) in the SCN1A protein. Both amino acid substitutions might disrupt these highly conserved regions in species from drosophila to human, leading to dysfunction of the protein. p.V1612I and p.C1756G were determined as disease-causing mutations due to their absence in the control population., Conclusion: The first cases of SMEI and SMEB are reported in South-East Asian populations. Two novel SCN1A mutations are also identified in these patients, p.V1612I and p.C1756G, which may lead to neuronal excitability or convulsions.

Background: There are significant differences in the prevalence and severity of neonatal jaundice among various populations. Recently, it has been reported that a mutation of the UGT1A1 gene, glycine to arginine at codon 71 (G71R), is related to the development of neonatal jaundice in East Asian populations. However, whether the G71R mutation contributes to the high incidence of neonatal jaundice in different Asian populations remains unknown. The authors screened for this mutation in the Javanese-Indonesian and Malay-Malaysian populations., Methods: One hundred and thirty-six subjects were enrolled in this study: 68 Javanese-Indonesian adults and 68 Malay-Malaysian newborns (32 with jaundice and 36 without jaundice). Denaturing high-performance liquid chromatography (DHPLC) was used to screen for the G71R mutation, and the results were confirmed by nucleotide sequencing analysis., Results: With DHPLC, the authors easily and clearly detected seven subjects carrying the G71R mutation: two Javanese-Indonesian adults and five Malay-Malaysian newborns. In the 68 Javanese-Indonesian adults, the genotype distribution for G71R mutation was 66 G/G, two G/R and no R/R genotypes, and the mutated allele frequency was 0.015. In the 68 Malay-Malaysian newborns, genotype distribution for the mutation was 63 G/G, five G/R and no R/R genotypes, and the mutated allele frequency was 0.037. The genotype distributions did not differ significantly between the newborns with jaundice and those without jaundice., Conclusion: The G71R mutation is present, but very rare, in Javanese-Indonesians and Malay-Malaysians. Thus, G71R mutation may not contribute to the high incidence of the neonatal jaundice in South-east Asian populations. DHPLC analysis is a very useful method for detecting the G71R mutation.

Background: Frontoethmoidal encephalocele (FEE) is a neural tube defect (NTD) characterized by a congenital bone defect in the anterior cranium and herniation of the intracranial mass through the defect. The C677T mutation in the 5,10-methylenetetrahydrofolate reductase gene (MTHFR) has been reported as a genetic risk factor for spina bifida. However, the role of the MTHFR in the pathogenesis of FEE remains to be clarified., Methods: A hospital-based survey of FEE patients who were referred to the Department of Neurosurgery and Plastic Surgery, Malang General Hospital, East Java, Indonesia was conducted. Genetic screening of MTHFR substitutions in 13 patients and eight mothers from 11 affected families were performed using a combination of polymerase chain reaction (PCR), denaturing high-performance liquid chromatography (DHPLC), and direct sequencing., Results: In total, 130 patients with FEE among 138 NTD patients (94.2%) were identified. The ratios of cranial encephalomeningocele to spinal meningocele (32 : 1) and of FEE to occipital encephalomeningocele (32 : 1) were higher than those in other populations. Five substitutions were detected in the MTHFR: C121T, C677T, C1060T, A1298C, and G1793A. No significant differences were found in the frequency of each nucleotide substitution between patients or mothers and controls. In addition, none of the subjects in this study were homozygous for T at nucleotide position 677., Conclusion: FEE is the most common form of NTD in East Java, Indonesia. Genetic analysis of 11 affected families suggests that the MTHFR gene is not associated with the development of FEE, although the number of FEE families analyzed in this study was very limited.

The presence of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene has been regarded as a genetic risk factor for coronary artery diseases and neural tube defects. Although the prevalence of this mutation has been reported from various ethnic populations, few data concerning Indonesian populations are available. We have investigated the frequency of the mutation in 68 Indonesian Javanese (residents of Java Island) and compared it with the data from 244 Japanese (residents of Honshu Island). The frequencies of the three genotypes in Javanese were C/C 0.84, C/T 0.16 and T/T 0.00, whereas those in Japanese were C/C 0.39, C/T 0.48 and T/T 0.13. The rarity of the T/T genotype in the Indonesian Javanese population may be due to malnutrition in pregnant women, because insufficient intake of folate is considered to be a survival disadvantage for fetuses with the T/T genotype. In conclusion, homozygosity for the C677T mutation in the MTHFR gene does not constitute a genetic risk factor for coronary artery diseases and neural tube defects in the Indonesian Javanese population.