Identification of a mutation in the human raloxifene response element of the transforming growth factor-3 gene

The human transforming growth factor-3 (TGF-3) is an important cytokine to maintain bone mass by inhibiting osteoclast differentiation. Recently raloxifene response element (RRE), a new enhancer with a polypurine sequence for estrogen receptor (ER)-mediated gene activation, was identified on the TGF-3 gene. Functional analysis of the RRE-mediated pathway has shown that this would be an important pathway for bone preserving effect. We found a novel mutation in the RRE sequence by single-strand conformational polymorphism analysis in one of 200 Korean women. Cloning and sequencing revealed a heterozygote in which one allele had an insertion of 20 nucleotides (AGAGAGGGAGAGGGAGA GGG) between nucleotide +71 and +72 and a point mutation at nucleotide +75 (G-A transition), and the other allele had normal sequence. The insertion was a nearly perfect tandem duplication of the wild type DNA sequence. The bone mineral density of the affected woman was not much lower than that of age-matched controls. Transient transfection of the mutant allele showed no significantly different activity compared with that of the wild type allele. These observations suggest that the heterozygote variation of the RRE sequence seems not to be operative in determination of bone mass.

Relationship between maternal weight gain and newborn's birthweight in women with normal glucose tolerance and gestational diabetes / 대한산부인과학회잡지

OBJECTIVE: The purpose of this study was to determine the independent factors that predict neonatal birthweight and find the relationship between maternal weight gain and neonatal birthweight in women with normal glucose tolerance (NGT) and gestational diabetes mellitus (GDM). METHODS: Forty-six women with GDM and one hundred fifty women with NGT were included in the study. All subjects had singleton pregnancies and no medical diseases that may affect the fetal growth and were certain of gestational age by early ultrasonography. Maternal weight at each prenatal visit was recorded and neonatal anthropometic measurement was done within 2 days of birth. RESULTS: The average rate of weight gain (kg/week) in NGT was lowest during the first trimester (0.09 +/-0.10), peaked during the second trimester (0.52+/-0.14), and slowed after 34 gestational weeks (0.46+/-0.26). In women with GDM, the average rate of weight gain was also lowest during the first trimester (0.18+/-0.23), but it was twofold higher compared with women with NGT. There was a significant decrease of the rate of weight gain after 28 gestational weeks in women with GDM. Total weight gain during pregnancy was 3.4 kg less in women with GDM. Neonatal birthweight was correlated with maternal weight gain and the rate of weight gain during 14-27 and 28-33 weeks in NGT. However, birthweight was correlated with maternal weight gain and the rate of weight gain during the first trimester and 14-27 weeks in GDM. CONCLUSION: This result suggests that the women with GDM who have greater weight gain during the first and the second trimester have a increased risk of excessive fetal growth. Thus strict glycemic control during pregnancy is needed especially in these women.

A Case of the McCune: Albright Syndrome Associated with Activating Mutations of Stimulatory G Protein / 대한내분비학회지

McCune-Albright syndrome (MAS) is a sporadic disease classically including polyostotic fibrous dysplasia, cafe -au-lait spots, sexual precocity, and other hyperfunctional endocrinopathies. Recent investigations suggest an etiological role for activating embryonic somatic missense mutations in the gene for the a subunit of Gs (Gsa), the G protein that stimulates adenylyl cyclase. DNA from bone, ovary, and blood was analyzed by using polymerase chain reaction and sequenced. A embryological somatic mutation of Gsa gene encoding substitution of a Cys for Arg at amino acid 201 from cells of dysplastic bone and ovary was observed, and the distribution of mutant gene reveals mosaic pattern. We report a case of McCune-Albright syndrome with an activating mutation at codon 201 of Gsa subunit on ovary and bone tissue that was experienced recently.