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Yoshio Makita

Publications and source records attributed to Yoshio Makita.

15 recordsLinked to original sources
PubMed2006

Mutation of the follicle-stimulating hormone receptor gene 5'-untranslated region associated with female hypertension.

Inactivating mutations in the follicle-stimulating hormone receptor (FSHR) gene have been reported to cause hereditary hypergonadotropic ovarian failure. It has been found recently that the FSHR knockout mouse exhibits hypertension. The aim of the present study was to investigate the association between polymorphisms in the human FSHR gene and essential hypertension (EH) by using single nucleotide polymorphisms (SNPs). We selected 5 SNPs in the gene (rs1394205, rs2055571, rs11692782, rs1007541, and rs2268361) and performed 2 genetic case-control studies in different populations. A confirmative case-control study was performed using 1035 EH patients and 1058 age-matched controls. Transcriptional activities were measured with a luciferase assay system. The first case-control study found that the A allele of rs1394205 was significantly higher in EH females (P=0.010). In addition, in the confirmative case-control study, there was a significant difference for this SNP between female normotensive subjects (44.5%) and EH patients (50.7%) (P=0.043). Multiple logistic regression analysis in female subjects also revealed a significant association of subjects with the A allele of rs1394205 with EH (P=0.033), with the odds ratio calculated as 1.68 (95% CI: 1.04 to 2.73). Transcriptional activity of the A allele was 56+/-8% (mean+/-SD) of that observed for the G-type allele (P=0.001). Serum estradiol levels were significantly lower in patients with the A/A genotype than in patients without the A/A genotype (P=0.004). The SNP in the 5'-untranslated region of the FSHR gene affects levels of transcriptional activity and is a susceptibility mutation of EH in women.

5' Untranslated Regions↗
PubMed2006

Spine and rib abnormalities and stature in spondylocostal dysostosis.

STUDY DESIGN: A retrospective study of radiographic and clinical findings of spondylocostal dysostosis. OBJECTIVE: To determine the features of spondylocostal dysostosis diagnosed using consistent diagnostic criteria. SUMMARY OF BACKGROUND DATA: To our knowledge, no clear definition of spondylocostal dysostosis exists, and little information is available regarding its clinical or radiographic features. METHODS: We defined spondylocostal dysostosis as a congenital spinal disorder consisting of >or=2 vertebral anomalies associated with rib anomalies, without crab-like chest. For 30 patients, including 12 males and 18 females, who met these criteria, we evaluated vertebral and rib anomalies, birth and present body height, and associated anomalies. There were only 2 familial cases. RESULTS: Features of spondylocostal dysostosis were: (1) anomalies involved the thoracic region in all cases; many also involved the cervical spine; (2) most patients had >or=4 vertebral anomalies; (3) frequent vertebral anomalies were butterfly vertebra, hemivertebra, complete block, and unilateral bar, which were associated with both rib absence and fusion; (4) short stature was not always present at birth; and (5) complete block was 1 factor identified as being related to short stature after 12 years of age. CONCLUSION: Several features of sporadic spondylocostal dysostosis disorder were determined, including new findings related to body height.

Abnormalities, Multiple↗
PubMed2006

BAC array CGH reveals genomic aberrations in idiopathic mental retardation.

Array using 2,173 BAC clones covering the whole human genome has been constructed. All clones spotted were confirmed to show a unique signal at the predicted chromosomal location by FISH analysis in our laboratory. A total of 30 individuals with idiopathic mental retardation (MR) were analyzed by comparative genomic hybridization using this array. Three deletions, one duplication, and one unbalanced translocation could be detected in five patients, which are likely to contribute to MR. The constructed array was shown to be an efficient tool for the detection of pathogenic genomic rearrangements in MR patients as well as copy number polymorphisms (CPNs).

Chromosome Aberrations↗
PubMed2006

Phenotypic spectrum of CHARGE syndrome with CHD7 mutations.

CHD7 gene mutations were identified in 17 (71%) of 24 children clinically diagnosed to have CHARGE syndrome (C, coloboma of the iris or retina; H, heart defects; A, atresia of the choanae; R, retardation of growth and/or development; G, genital anomalies; and E, ear abnormalities). Colobomata, hearing loss, laryngomalacia, and vestibulo-cochlear defect were prevalent. Molecular testing for CHD7 enables an accurate diagnosis and provides health anticipatory guidance and genetic counseling to families with CHARGE syndrome.

Abnormalities, Multiple↗
PubMed2005

Phenotypic consequences of genetic variation at hemizygous alleles: Sotos syndrome is a contiguous gene syndrome incorporating coagulation factor twelve (FXII) deficiency.

PURPOSE: We tested the hypothesis that Sotos syndrome (SoS) due to the common deletion is a contiguous gene syndrome incorporating plasma coagulation factor twelve (FXII) deficiency. The relationship between FXII activity and the genotype at a functional polymorphism of the FXII gene was investigated. METHODS: A total of 21 patients including those with the common deletion, smaller deletions, and point mutations, and four control individuals were analyzed. We examined FXII activity in patients and controls, and analyzed their FXII 46C/T genotype using direct DNA sequencing. RESULTS: Among 10 common deletion patients, seven patients had lower FXII activity with the 46T allele of the FXII gene, whereas three patients had normal FXII activity with the 46C allele. Two patients with smaller deletions, whose FXII gene is not deleted had low FXII activity, but one patient with a smaller deletion had normal FXII. Four point mutation patients and controls all had FXII activities within the normal range. CONCLUSION: FXII activity in SoS patients with the common deletion is predominantly determined by the functional polymorphism of the remaining hemizygous FXII allele. Thus, Sotos syndrome is a contiguous gene syndrome incorporating coagulation factor twelve (FXII) deficiency.

Adolescent↗
PubMed2005

Comprehensive screening of CREB-binding protein gene mutations among patients with Rubinstein-Taybi syndrome using denaturing high-performance liquid chromatography.

Mutations in the CREBBP (CREB-binding protein gene) cause Rubinstein-Taybi syndrome (RSTS). At present, however, genetic testing of CREBBP is not commonly applied in clinical settings because the currently available assays are technically and financially demanding, mainly because of the size of the gene. In the present study, we took advantage of a highly sensitive and specific, automated denaturing high-performance liquid chromatography (DHPLC) technique. First, we developed a DHPLC-based protocol to analyze the entire coding region of CREBBP. Second, we analyzed genetic samples from 21 RSTS patients using DHPLC. The coding region was amplified by 41 primer pairs, all of which have the same cycling conditions, aliquoted on a 96-well format PCR plate. In this manner, all the exons were simultaneously amplified using a single block in a PCR machine. We then wrote a computer script to analyze all the PCR amplicons generated from various portions of the CREBBP gene in a serial manner at optimized conditions determined individually for each amplicon. Heterozygous CREBBP mutations were identified in 12 of the 21 patients: five frameshift mutations, three nonsense mutations, two splice-site mutations, and two missense mutations. The resulting detection rate of 57% was comparable to the outcome of previous studies. The relatively high detection rate in the present study demonstrates the enhanced sensitivity of the DHPLC-based mutation analysis, as exemplified by mutation analyses of other genes. The implementation of similar methodologies for other dysmorphic syndromes will help medical geneticists to confirm their clinical impressions and to provide accurate genetic counseling for patients and their families.

CREB-Binding Protein↗
PubMed2004

Novel SBDS mutations caused by gene conversion in Japanese patients with Shwachman-Diamond syndrome.

Shwachman-Diamond syndrome (SDS; OMIM 260400) is an autosomal recessive disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction and metaphyseal chondrodysplasia. SDS is caused by mutations in SBDS, an uncharacterized gene. A previous study in SDS patients largely of European ancestry found that most SBDS mutations occurred within a approximately 240-bp region of exon 2 and resulted from gene conversion due to recombination with a pseudogene, SBDSP. It is unknown, however, whether these findings are applicable to other ethnic groups. To address this question, we examined SBDS mutations in six Japanese families with SDS by direct sequencing. We identified compound heterozygous mutations in four families: two were recurrent (96-97insA, 258+2T>C), and three were novel [292-295delAAAG, (183-184TA>CT +201A>G), (141C>T+183-184TA>CT+201A>G)] mutations. Most of these mutations also appear to result from gene conversion, but the conversion events occurred at various sites between intron 1 and exon 3. Thus, gene conversion mutations in SBDS are common to different ethnic groups, but they are not confined to a limited region of the gene.

Alleles↗
PubMed2003

Fifty microdeletions among 112 cases of Sotos syndrome: low copy repeats possibly mediate the common deletion.

Sotos syndrome (SoS) is an autosomal dominant overgrowth syndrome with characteristic craniofacial dysmorphic features and various degrees of mental retardation. We previously showed that haploinsufficiency of the NSD1 gene is the major cause of SoS, and submicroscopic deletions at 5q35, including NSD1, were found in about a half (20/42) of our patients examined. Since the first report, an additional 70 SoS cases consisting of 53 Japanese and 17 non-Japanese have been analyzed. We found 50 microdeletions (45%) and 16 point mutations (14%) among all the 112 cases. A large difference in the frequency of microdeletions between Japanese and non-Japanese patients was noted: 49 (52%) of the 95 Japanese patients and only one (6%) of the 17 non-Japanese had microdeletions. A sequence-based physical map was constructed to characterize the microdeletions. Most of the microdeletions were confirmed to be identical by FISH analysis. We identified highly homologous sequences, i.e., possible low copy repeats (LCRs), in regions flanking proximal and distal breakpoints of the common deletion, This suggests that LCRs may mediate the deletion. Such LCRs seem to be present in different populations. Thus the different frequency of microdeletions between Japanese and non-Japanese cases in our study may have been caused by patient-selection bias.

Carrier Proteins↗
PubMed2003

Haplotype analysis of the human collectin placenta 1 (hCL-P1) gene.

Collectins are a family of C-type lectins found in vertebrates. These proteins have four regions, a relatively short N-terminal region, a collagen-like region, an alpha-helical coiled coil, and a carbohydrate recognition domain. Collectins are involved in host defense through their ability to bind carbohydrate antigens on microorganisms. Type A scavenger receptors are classical-type scavenger receptors that also have collagen-like domains. We previously described a new scavenger receptor, collectin from placenta [collectin placenta 1 (CL-P1)]. CL-P1 is a type II membrane protein with all four regions. We found that CL-P1 can bind and phagocytize both bacteria and yeast. In addition to that, it reacts with oxidized low-density lipoprotein (LDL) but not with acetylated LDL. These results suggest that CL-P1 might play important roles in host defenses and/or atherosclerosis formation. One rational strategy to study the role of CL-P1 in these pathological conditions would be to perform a haplotype association study using human samples. As a first step for this strategy, we analyzed the haplotype structure of the CL-P1gene. By sequencing the CL-P1 gene in ten Japanese volunteers, we identified five single-nucleotide polymorphisms (SNPs) with a minor allele frequency of at least 29%. To obtain SNPs in the 5'-upstream region of the gene, we screened a total of 20 SNPs described in the database and finally picked up one SNP for the present study. Thus, a total of six SNPs, one in the 5'-upstream region, two in intron 2, one in exon 5, and two in exon 6, were used to analyze the haplotype structure of the gene, with DNAs derived from 54 individuals (108 alleles). The analysis revealed that only two of six SNPs showed significant linkage disequilibrium ( r(2) > 0.5) with each other. This haplotype information may be useful in disease-association studies in which a contribution of the CL-P1 gene has been suspected, especially in immunological disturbance or atherosclerosis. Two SNPs in exon 6, both leading to amino acid substitutions, could be candidates for influencing disease susceptibility.

Amino Acid Substitution↗
PubMed2002

Haploinsufficiency of NSD1 causes Sotos syndrome.

We isolated NSD1 from the 5q35 breakpoint in an individual with Sotos syndrome harboring a chromosomal translocation. We identified 1 nonsense, 3 frameshift and 20 submicroscopic deletion mutations of NSD1 among 42 individuals with sporadic cases of Sotos syndrome. The results indicate that haploinsufficiency of NSD1 is the major cause of Sotos syndrome.

Acromegaly↗
PubMed2002

Camurati-Engelmann disease type II: progressive diaphyseal dysplasia with striations of the bones.

We recently found mutations of the transforming growth factor beta 1 (TGF-beta1) gene (TGFB1) in 9 families, in which progressive diaphyseal dysplasia (Camurati-Engelmann disease) is segregating [Kinoshita et al., 2000: Nat Genetics 26:19-20]. During the study, we encountered two unrelated girls, aged 17 and 11 years, who had clinical manifestations of the disorder, such as marfanoid habitus, waddling gait, muscular weakness, intense leg pain, flexion contracture of the hip and knee joints, delayed sexual development, increased serum alkaline phosphatase levels, and increased erythrocyte sedimentation rates. Radiographic studies in the two girls demonstrated not only diaphyseal dysplasia (cortical thickening of the diaphyses) resembling that of progressive diaphyseal dysplasia but also metaphyseal expansion of the long bones, coarse and thick trabeculae of the long and short tubular bones, striations in the spinal, pelvic, and long bones, and cranial sclerosis restricted to the petromastoid regions. These radiographic changes were overall identical with those seen in hyperostosis generalisata with striations of the bones rather than those in progressive diaphyseal dysplasia. Polymerase chain reaction-direct sequencing of all exons and their flanking regions of TGFB1 did not detect any mutations. PCR-single strand conformational polymorphism analysis of the TGF-beta type 1 receptor gene (TGFBR1) did not demonstrate any aberrant DNA fragments. We concluded from these findings that the two girls we described belong to a unique entity distinct from either of the two disorders.

Activin Receptors, Type I↗
PubMed2002

Linkage and association analyses of the osteoprotegerin gene locus with human osteoporosis.

Osteoprotegerin (OPG), a secreted glycoprotein and a member of the tumor necrosis factor receptor superfamily, is considered to play an important role in the regulation of bone resorption by modifying osteoclast differentiation. Overexpression of OPG in mice has been reported to result in osteopetrosis, whereas targeted disruption of OPG in mice has been associated with osteoporosis. Accordingly, OPG could be a strong candidate gene for susceptibility to human osteoporosis. Here, we analyzed whether OPG is involved in the etiology of osteoporosis using both linkage and association analyses. We recruited 164 sib pairs in Gunma prefecture, which is located in the central part of Honshu (mainland Japan), for a linkage study, and 394 postmenopausal women in Akita prefecture, which is in the northern part of Honshu, for an association study. We identified two microsatellite polymorphisms in the linkage study, and six single-nucleotide polymorphisms (SNPs) in the OPG region for the association study. Although, no evidence of significant linkage between OPG and osteoporosis was found, a possible association of one SNP, located in the promoter region of the gene, was identified. A haplotype analysis with the six SNPs revealed that four major haplotypes account for 71% of the alleles in the Japanese population.

Base Sequence↗
PubMed2002

Methylenetetrahydrofolate reductase genotype, vitamin B12, and folate influence plasma homocysteine in hemodialysis patients.

Hyperhomocysteinemia, a well-recognized cardiovascular risk factor, is frequent in hemodialysis (HD) patients. A common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, C-->T substitution at nucleotide 677, is associated with homocysteine (Hcy) level elevation. We examined whether three factors involved in the methionine cycle could influence plasma Hcy concentrations in HD patients: MTHFR polymorphism; vitamin B12, an essential cofactor; and folate, the substrate. In a cross-sectional study, serum vitamin B12, folate, and plasma Hcy were measured and MTHFR genotyping was performed in 534 HD patients. Effects of MTHFR genotypes, vitamin B12, and folate on plasma Hcy levels were examined in 450 HD patients not administered vitamin B12 or folate. To examine the effect of vitamin B12 on plasma Hcy concentrations, we compared plasma Hcy concentrations in HD patients with and without vitamin B12 supplementation. To examine whether functional vitamin B12 deficiency exists even in HD patients with normal vitamin B12 concentrations, 15 HD patients (serum vitamin B12 concentrations, 250 to 2,100 pg/mL) were treated with vitamin B12 (mecobalamin, 1.5 mg/d) for 8 weeks. Serum concentrations of methylmalonic acid (MMA) and vitamin B12 were measured. Hcy levels were higher and folate levels were lower in patients with the TT and CT genotypes compared with patients with the CC genotype. Analysis of covariance to determine independent predictors of high Hcy levels identified low serum vitamin B12 and folate levels and high albumin (Alb) levels in CC-genotype patients, low folate levels and high Alb levels in CT-genotype patients, and low folate levels in TT-genotype patients. Plasma Hcy levels were lower in CC- and CT-genotype patients with vitamin B12 supplementation than in those without supplementation. Vitamin B12 supplementation for 8 weeks significantly reduced MMA concentrations in HD patients with normal serum vitamin B12 concentrations. These results indicate that MTHFR genotype influences the correlation of Hcy level with vitamin B12 and folate levels in HD patients. Functional vitamin B12 deficiency may exist, even in HD patients with normal vitamin B12 concentrations. The efficacy of vitamin B12 and folate supplementation on plasma Hcy levels may depend on MTHFR genotype.

Cross-Sectional Studies↗