Novel splice site mutation in the fumarate hydratase (FH) gene is associated with multiple cutaneous leiomyomas in a Japanese patient.

Cutaneous leiomyoma is a benign skin tumor that originates from the smooth muscle, such as the arrector pili muscle of the hair follicles. Familial cases with multiple cutaneous leiomyomas exist, which typically show an autosomal dominant inheritance trait. Most patients with the disease are known to carry heterozygous germ line mutations in the fumarate hydratase (FH) gene and can be complicated by tumors in internal organs, especially uterine leiomyoma and renal cell cancer in high frequency. In this study, we identified a Japanese male patient with multiple cutaneous leiomyomas and found a novel heterozygous splice site mutation, c.738 + 2T>A, in the FH gene of the patient, which was unexpectedly inherited from his unaffected father. Further analysis demonstrated loss of heterozygosity in the tumor tissue, which resulted in a hemizygote state of the mutant allele. Expression studies with the tumor tissue showed that the mutation led to skipping of exon 5 at mRNA levels, which was predicted to cause an in-frame deletion of FH protein (p.Ser186_Gln246del). The protein structure analysis strongly suggested that the deletion would severely disrupt the conformation of the FH protein including the substrate-binding domain, and thus would severely affect the expression and the function. Our findings further disclose the molecular basis of multiple cutaneous leiomyomas and also provide precious information to the mutation carriers in the family for an early diagnosis of renal cell cancer in the future.

Undergraduate dental English education in Japanese dental schools.

Dental schools in Japan are among many worldwide whose medium of instruction is not in English. With advances in science, technology, and communication, the demand for the globalization of professions increases. At present, dental schools in Asia, the Middle East, and Europe have started revising their dental curricula to either include English courses for dentistry or offer a full English dental curriculum. In Japan, dental English courses started to be introduced into curricula in the early 1990s. However, a survey conducted in 1999 found that English courses were not offered in Japan's twenty-nine dental schools and there was no consensus as to what such courses should include or when and how they should be taught. Ten years after that survey, the survey results reported in this article found that the problems reported in the 1999 survey still exist. Additionally, there are still differences among schools offering English courses in terms of the timing and contents of the courses. Since teachers and school officials will have an important role in curriculum development, this article recommends that a fact-finding meeting with educators, school, and education officials be initiated to discuss, develop, and implement a core curriculum for these dental English courses.

Mutation analysis of the IL36RN gene in 14 Japanese patients with generalized pustular psoriasis.

Generalized pustular psoriasis (GPP) is a rare, potentially life threatening, and aggressive form of psoriasis, which is characterized by sudden onset with repeated episodic skin inflammation leading to pustule formation. Familial GPP is known to be caused by recessively inherited mutations in the IL36RN gene, which encodes interleukin 36 receptor antagonist (IL-36Ra). In this article, we performed mutation analysis of the IL36RN gene in 14 Japanese patients with GPP, and identified mutations in two of these patients analyzed. One patient was compound heterozygous for mutations c.115+6T>C and c.368C>G (p.Thr123Arg), whereas the other carried compound heterozygous mutations c.28C>T (p.Arg10*) and c.115+6T>C in the IL36RN gene. Expression studies using total RNA from the patients' skin revealed that the mutation c.115+6T>C resulted in skipping of exon 3, leading to a frameshift and a premature termination codon (p.Arg10Argfs*1). The protein structure analysis suggested that the missense mutation p.Thr123Arg caused misfolding and instability of IL-36Ra protein. In vitro studies in cultured cells showed impaired expression of the p.Thr123Arg mutant IL-36Ra protein, which failed to antagonize the IL-36 signaling pathway. Our data further underscore the critical role of IL36RN in pathogenesis of GPP.

Culture-based PCR analysis of plaque samples of Japanese school children to assess the presence of six common cariogenic bacteria and its association with caries risk.

The aim of the study was to assess the presence of six common cariogenic bacteria from Cariostat-inoculated plaque samples of Japanese elementary school children through PCR analysis and check its associations with caries risk testing the validity of Cariostat as a caries risk assessment tool. This epidemiological school-based study investigated plaque samples of 399 Japanese elementary school children. Assessed using the Cariostat, 48.2% of the children had high caries risk. DNA detection of Streptococcus mutans, Streptococcus sobrinus, Streptococcus salivarius, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus fermentum and both S. mutans and S. sobrinus was seen in 65.2%, 24.1%, 69.7%, 17.5%, 7.8%, 19.3%, and 17.3% of the participants, respectively. Except for S. salivarius, the presence of all other investigated bacteria resulted in a statistically significant increase among the proportion of subjects with high caries risk. Caries risk assessed using Cariostat was significantly influenced by the presence of cariogenic bacteria. Being a selective medium for cariogenic bacteria, the Cariostat can be a useful and direct source of cariogenic bacterial DNA for PCR analysis while effectively assessing caries risk.

Skin metastasis of dermatofibrosarcoma protuberans with distinct morphological features, confirmed by COL1A1-PDGFB fusion gene analysis.

We discuss a metastatic dermatofibrosarcoma protuberans on the occiput of a 53-year-old man whose initial tumor appeared on his forehead 23 years previously. The pathology of the tumor that recurred at the initial site was fibrosarcomatous dermatofibrosarcoma protuberans, whereas the metastatic tumor was a pigmented dermatofibrosarcoma protuberans, the so-called Bednar tumor. Because both tumors possessed the identical chimeric COL1A1-PDGFB fusion gene, the metastatic nature of the occipital tumor was confirmed.

Using a caries activity test to predict caries risk in early childhood.

BACKGROUND: The authors conducted a two-year longitudinal study to show the predictive abilities of a caries activity test (Cariostat, Dentsply-Sankin, Tokyo), and to include the predicted screening indexes that were based on previous caries activity test results and lifestyle factors that influence caries activity. METHODS: The subjects were 1,206 children born in 2000. These children participated in health examinations at 18 months, 2 years and 3 1/2 years of age at Kurashiki-City Public Health Center in Kurashiki-City, Japan. Two of the authors performed caries activity tests at 18-month and 2-year examinations. Questionnaires regarding the patient's lifestyle were mailed to each participant's parents or guardians. The authors analyzed these questionnaires to evaluate lifestyle factors that made participants susceptible to caries. RESULTS: A caries activity test score at 18 months of age not only reflected caries incidence but also predicted caries incidence and screening results in 2- and 3 1/2-year-old children. A caries activity test score at 2 years of age both reflected and predicted children's caries incidence and screening results at 3 1/2 years of age. Breast-feeding and use of the bottle to intake liquids other than water produced significant caries susceptibility in 18-month-old children. Additionally, increased frequency and total time of sucrose intake put 2-year-old children at high risk of developing caries and failure of parental brushing produced a high risk in 3 1/2-year-old children. CONCLUSIONS: A caries activity test could predict 3 1/2-year-old children's caries risk based on 18-month and 2-year-old test results. Early weaning, less sucrose intake and toothbrushing by parents were effective in reducing a child's caries risk. CLINICAL IMPLICATIONS: The caries activity test is more useful than oral examination because it can indicate the need for caries-preventive treatment before a carious lesion actually is manifest.

Cariogenic bacteria and caries risk in elderly Japanese aged 80 and older with at least 20 teeth.

OBJECTIVES: To assess caries risk and check the presence of four commonly found oral cariogenic bacteria in "8020" achievers. DESIGN: Initial report based on Japan's newly implemented "8020" campaign, which aims to promote health and awareness in older people. Simply stated, the goal is, at 80 years, to maintain 20 teeth. SETTING: Healthy community-dwelling elderly individuals of Okayama Prefecture, Japan. PARTICIPANTS: One hundred sixty individuals aged 80 and older with 20 of their own natural teeth. MEASUREMENTS: General and oral health conditions, caries risk assessment using the Cariostat method, and polymerase chain reaction (PCR) detection of four oral cariogenic bacteria. RESULTS: The participants had an average of 24.7 teeth, of which 12.1 were sound, 12.2 were treated, and 0.4 were untreated. Based on Cariostat scores, 64.4% had low caries risk. Using PCR, Streptococcus mutans, S. sobrinus, Lactobacillus casei, and L. plantarum were detected in 51.3%, 23.1%, 40%, and 25% of the participants, respectively. S. mutans (P<.001), S. sobrinus (P=.002), L. casei (P<.001), and L. plantarum (P=.001) deoxyribonucleic acid band was detected more in participants with high caries risk scores. CONCLUSION: Participants with low caries risk scores had low prevalence of cariogenic bacteria, 20 or more sound teeth, and fewer missing teeth. Incorporating caries risk assessment, using the Cariostat and PCR analysis, in the "8020" campaign in health systems worldwide will contribute to a better life for the aging society, initiate research interest regarding the program, and improve current health policies.

Mutations in the desmoglein 4 gene are associated with monilethrix-like congenital hypotrichosis.

The gene encoding human desmoglein 4 (DSG4) was recently cloned, and a mutation in this gene has been reported in several consanguineous Pakistani families affected with localized autosomal recessive hypotrichosis (LAH). In addition, various mutations in the Dsg4 gene have been identified in animal models of hypotrichosis that share a characteristic phenotype called "lanceolate hair". To date, the features of the hair-shaft anomaly in patients with LAH have not been well described. We report a Japanese patient affected with congenital hypotrichosis that was originally diagnosed as monilethrix because she had a hair-shaft abnormality that resembled moniliform hair. However, no mutations were found in the type II hair keratin genes, hHb1, hHb3, and hHb6, whose mutations cause monilethrix. Instead, we identified novel compound heterozygous mutations in the DSG4 gene of our patient. On the maternal allele is a novel S192P transition within the extracellular cadherin II domain of DSG4; on the paternal allele is a novel 2039insT mutation leading to the generation of unstable transcripts. Here we present the observation that mutations in the DSG4 gene can cause monilethrix-like congenital hypotrichosis. Based on our findings, we propose that LAH and monilethrix could overlap.

Size polymorphisms in the human ultrahigh sulfur hair keratin-associated protein 4, KAP4, gene family.

Hair keratin-associated proteins (KAP) are a major structural component of the hair fiber. In humans, five clusters of KAP genes have been identified, leading to the isolation of more than 80 individual KAP members. Of these, a cluster of high/ultrahigh sulfur KAP has been characterized on chromosome 17q12-21. Within this cluster, however, there was an incompletely sequenced region in which the ultrahigh sulfur KAP4 genes were located. A recently reported human bacterial artificial chromosome clone, AC100808, finally covered the gap, which enabled us to characterize the complete set of KAP4 genes in this cluster. Analysis of the nucleotide sequences of AC100808, together with PCR amplification, allowed us to identify numerous size polymorphisms in the KAP4 genes, which were mainly due to variations in the sequences encoding cysteine-rich repeat segments. Taken together, the data indicate that the polymorphic alleles of the KAP4 genes may have arisen through intragenic deletion and/or duplication of sequences encoding the repeat structures during evolution.