We analyzed the bilirubin uridine diphosphate‐glucuronosyltransferase (B‐UGT) gene in 42 Japanese newborns with hyperbilirubinemia and determined that 21 infants were heterozygous while 3 was homozygous for Gly71Arg. Allele frequency of Gly71Arg was 0.32 in newborns with hyperbilirubinemia, which was significantly higher than 0.13 in healthy Japanese controls. This mutant allele is also prevalent among Korean and Chinese healthy controls with a frequency of 0.23 in both populations. However, this mutation was not detected in 50 healthy German controls. These data suggest that the high frequency of the Gly71Arg mutation of the B‐UGT gene is associated with high incidence of neonatal hyperbilirubinemia in Japanese, Korean and Chinese populations.

Early-onset epileptic encephalopathies (EOEE) are severe neurological disorders characterized by frequent seizures accompanied by developmental regression or retardation. Whole-exome sequencing of 12 patients together with five pairs of parents and subsequent Sanger sequencing in additional 328 EOEE patients identified two de novo frameshift and one missense mutations in SLC35A2 at Xp11.23, respectively. The three patients are all females. X-inactivation analysis of blood leukocyte DNA and mRNA analysis using lymphoblastoid cells derived from two patients with a frameshift mutation indicated that only the wild-type SLC35A2 allele was expressed in these cell types, at least in part likely as a consequence of skewed X-inactivation. SLC35A2 encodes a UDP-galactose transporter (UGT), which selectively supplies UDP-galactose from the cytosol to the Golgi lumen. Transient expression experiments revealed that the missense mutant protein was correctly localized in the Golgi apparatus. In contrast, the two frameshift mutant proteins were not properly expressed, suggesting that their function is severely impaired. Defects in the UGT can cause congenital disorders of glycosylation. Of note, no abnormalities of glycosylation were observed in three serum glycoproteins, which is consistent with favorably skewed X-inactivation. We hypothesize that a substantial number of neurons might express the mutant SLC35A2 allele and suffer from defective galactosylation, resulting in EOEE.

We present a reliable, rapid, and economical multiplex amplified product-length polymorphism (APLP) method for analyzing the haplogroup-diagnostic mitochondrial single-nucleotide polymorphisms (mtSNPs) in East Asian populations. By examining only 36 haplogroup-specific mtSNPs in the coding region by using four 9-multiplex polymerase chain reaction (PCR) and subsequent electrophoresis, we could safely assign 1815 individuals from 8 populations of Japanese, Korean, Chinese, and Germans to 45 relevant haplogroups. This multiplex APLP analysis of coding-region mtSNPs for haplogrouping is especially useful not only for molecular phylogenetic studies but also for large-scale association studies due to its rapid and economical nature. This is the first panel of mtSNPs in the coding region to be used for haplogrouping of East Asian populations.

The human orosomucoid (ORM) is controlled by two closely linked loci, ORM1 and ORM2, and two tandem genes, AGP1 and AGP2, encoding the proteins produced by the two loci, have been cloned. In this study the molecular basis of ORM1 polymorphism was investigated. For the detection of mutations the products of the six exons of each gene, amplified by the polymerase chain reaction (PCR), were screened by single-strand conformation polymorphism analysis. Subsequently, the exons with an altered migration pattern were gene-specifically amplified by nested PCR. Sequencing of the gene-specific PCR products showed that the three common ORM1 alleles result from A-->G transitions at the codons for amino acid positions 20 in exon 1 and 156 in exon 5 of the AGP1 gene: ORM1*F1 was characterized by CAG (Gln) and GTG (Val), ORM1*F2, by CAG (Gln) and ATG (Met), and ORM1*S, by CGG (Arg) and GTG (Val). The phylogenesis of the genes encoding these three ORM1 alleles is discussed.