Clinical features and growth hormone receptor gene mutations of patients with Laron syndrome from a Chinese family / 中国当代儿科杂志

Laron syndrome is an autosomal recessive disorder caused by defects of growth hormone receptor (GHR) gene. It is characterized by severe postnatal growth retardation and characteristic facial features as well as high circulating levels of growth hormone (GH) and low levels of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3). This report described the clinical features and GHR gene mutations in 2 siblings with Laron syndrome in a Chinese family. Their heights and weights were in the normal range at birth, but the growth was retarded after birth. When they presented to the clinic, the heights of the boy (8 years old) and his sister (11 years old) were 80.0 cm (-8.2 SDS) and 96.6 cm (-6.8 SDS) respectively. They had typical appearance features of Laron syndrome such as short stature and obesity, with protruding forehead, saddle nose, large eyes, sparse and thin silky hair and high-pitched voice. They had higher basal serum GH levels and lower serum levels of IGF-I, IGFBP-3 and growth hormone binding protein (GHBP) than normal controls. The peak serum GH level after colonidine and insulin stimulations in the boy was over 350 ng/mL. After one-year rhGH treatment, the boy's height increased from 80.0 cm to 83.3 cm. The gene mutation analysis revealed that two patients had same homozygous mutation of S65H (TCA -->CCA) in exon 4, which is a novel gene mutation. It was concluded that a definite diagnosis of Laron syndrome can be made based on characteristic appearance features and serum levels of GH, IGF-I, IGFBP-3 and GHBP. The S65H mutation might be the cause of Laron syndrome in the two patients.

Association of the vitamin D receptor gene start codon polymorphism with delayed rickets / 中华儿科杂志

<p><b>OBJECTIVE</b>Delayed rickets is a special type of vitamin D deficiency, the occurrences of delayed rickets mainly relate to vitamin D deficiency, but whether there is hereditary susceptibility of children to development of delayed rickets is unknown. Recently some studies suggest that there is a significant association between vitamin D receptor gene (VDR) polymorphism and the metabolic diseases of bone. The present study aimed to explore the hereditary susceptibility of children to development of delayed rickets through studying the association of the vitamin D receptor gene start codon (VDRSC) polymorphism with delayed rickets.</p><p><b>METHODS</b>The diagnosis was based on clinical, biochemical and radiological data. The subjects were composed of three groups, the patient group had 30 children, the vitamin D deficiency group 35 children, and the control group 60 normal children. The VDRSC genotypes of the three groups were determined by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique.</p><p><b>RESULTS</b>There was significant difference in the frequencies distribution of VDRSC genotypes (chi(2) = 13.184, P = 0.010) and VDRSC alleles (chi(2) = 8.975, P = 0.011) among the three groups; the frequency of the FF genotype (56.7%) in the patient group was significantly higher than that in the control group (21.7%, P = 0.006) and that in the vitamin D deficiency group (22.9%, P = 0.002). The frequency of the F alleles in the patient group (70.0%) was significantly higher than that in the control group (48.3%, P = 0.006) and that in the vitamin D deficiency group (47.1%, P = 0.009). Multiple logistic regression analysis showed that FF genotype had a higher risk of delayed rickets (OR = 3.120), indicating that FF genotype may be significantly associated with delayed rickets.</p><p><b>CONCLUSION</b>There is the possibility that the VDRSC polymorphism might be important in determining the hereditary susceptibility of children to development of delayed rickets.</p>