Genes involved in human growth consist of major growth genes and minor growth genes. Major growth genes have fundamental effects on human growth, and their mutations cause growth failure (or overgrowth) which are recognizable as single gene disorders. Minor growth genes exert relative minor additive effects on human growth, and their combination is involved in the development of short (or tall) stature as a multifactorial trait. This review summarizes the current knowledge about the major and the minor growth genes, and refers to the recent molecular approach of identification of the growth genes.

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An increased incidence of Hashimoto thyroiditis has been reported in patients with Turner syndrome, but several cases of Graves' disease were also described ten to 20 years ago. We report the case of a patient with Turner syndrome who developed Graves' disease, 3 years after successful treatment with recombinant human growth hormone (GH). A diagnosis of Graves' disease was made and treatment with thiamazole was started, which resulted in normalization of the thyroid function. It is important to monitor thyroid function as well as growth parameters in patients with Turner syndrome.

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FGFR3 (fibroblast growth factor receptor 3) is a gene responsible for the most common form of osteodysplasia, achondroplasia, which results in extreme short stature. An allelic disorder, hypochondroplasia, however, presents with a much milder phenotype and is sometimes indistinguishable from idiopathic short stature. In this study, in order to test the possibility of the mildest end of hypochondroplasia being labeled as idiopathic short stature and the possibility of polymorphism of FGFR3 acting as one of the stature genes of normal individuals, we examined the prevalence of sequence alterations of the FGFR3 gene among individuals diagnosed clinically with idiopathic short stature. Sequencing analysis of all exons of the FGFR3 gene on 54 individuals with idiopathic short stature did not reveal any sequence variations related to the stature of the individuals. These results suggest that hidden hypochondroplasia among idiopathic short stature individuals is not a common occurrence and the contribution of polymorphism of the FGFR3 gene as a determinant of stature in normal individuals is small if any.

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In an attempt to study the roles of G-protein stimulatory subunit α (G_sα) in osteoblasts, we introduced an expression vector encoding G_sα into human osteoblastic cell line SaOS-2, and established the clones stably overexpressing G_sα (SaOS-2-G_sα). In SaOS-2-G_sα, the intracellular content of cyclic AMP (cAMP) was increased compared with the parental SaOS-2 cells. In addition, when treated with PTH[1-34], SaOS-2-G_sα exhibited more accumulation of intracellular cAMP compared with the parental cells, suggesting an increased responsiveness to PTH. We evaluated the proliferation rates of SaOS-2-G_sα and the parental SaOS-2 cells, and found that the proliferation was accelerated in SaOS-2-G_sα cells. Reverse transcription-polymerase chain reaction (RT-PCR) analyses exhibited the increased expression of Runx2, a transcription factor involved in osteoblast differentiation, in SaOS-2-G_sα cells. Finally, to examine the osteoblastic function in vivo, we inoculated SaOS-2-G_sα or parental SaOS-2 cells subcutaneously to immunocompromised nude mice. Although tumors in nude mice were not formed after inoculation of parental SaOS-2 cells, SaOS-2-G_sα cells proliferated in host animals leading to the formation of tumors with mineralized bone-like tissues. Taken together, these results suggest that the signals via G_sα play critical roles in the proliferation and osteogenic functions of osteoblasts.

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We investigated the changes of anthropometrical parameters in Japanese children with type 1 diabetes (T1DM) from birth to the onset of diabetes. One-hundred ninety-nine children (79 males and 120 females) diagnosed between 0-16 yr of age during the period between 1990 and 2003 were the subjects of this study. The subjects were categorized into 3 groups according to onset age (0-5 yr; n=74, 5-10 yr; n=61, 10-16 yr; n=64). At birth, the younger onset (<5) group had significant lower height and weight standard deviation score (SDS) compared with the older onset (5≤) group (p=0.01 and p=0.02, respectively). When the changes in height SDS from birth to onset were compared, height SDS at onset were significantly greater than those at birth in the younger onset group (p<0.001). However, no significant difference was observed in the other groups (p=0.95 and p=0.39). These results suggest that relatively small size at birth and accelerated growth after birth until the onset of diabetes may be a characteristic of Japanese T1DM children with younger onset and may further support the hypothesis that emphasizes accelerated growth and subsequent insulin resistance as a cause of earlier onset of T1DM.

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