Association of 45, X/46, XY mosaicism with disorders of sex development: the clinical analysis of 5 cases / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze clinical characteristics of children with 45, X/46, XY mosaicism and explore effective managements for them.</p><p><b>METHOD</b>Five children with 45, X/46, XY mosaicism were all in puberty period, of whom, three were female and two male. The standing height, weight and sexual development were measured. The levels of sex hormones, other endocrine parameters were also determined, and imaging examinations were performed.</p><p><b>RESULT</b>All the patients had disorders of sex development, of whom, 4 had short stature, and the HtSDs was -2.8 ± 1.1. The results of laboratory indexes suggested that 4 had hypergonadotropic hypogonadism, with the average level of LH (13.5 ± 5.8) IU/L and FSH (56.8 ± 37.4) IU/L. Imaging examinations revealed that 2 cases had cryptorchidism, 1 had immature uterus, 1 had testicular dysgenesis and 1 had normal testis. Three patients received rhGH treatment and 1 took gender assignment into account.</p><p><b>CONCLUSION</b>Patients with mosaic 45, X/46, XY karyotypes had a wide range of phenotypic manifestations, and disorders of sex development and short stature were the main clinical features. However, the disorders of sex development varied among these patients. And the management for them depends upon many factors and needs to be individualized based on the cooperation with different clinical departments.</p>

Genetic mutation analysis of a kindred with a patient suffering from 17 alpha-hydroxylase/17, 20-lyase deficiency / 中华儿科杂志

<p><b>OBJECTIVE</b>To detect CYP17A1 gene mutation in a patient with 17 alpha-hydroxylase/17, 20-lyase deficiency and her family members.</p><p><b>METHOD</b>Genomic DNA was extracted from the blood of the patient, her parents and twin sister. The 8 exons of CYP17A1 gene were amplified with polymerase chain reaction (PCR) and screened for mutations by sequencing.</p><p><b>RESULT</b>The analysis revealed that the patient was a compound heterozygote carrying two different inherited point mutations on CYP17A1 gene. They were nt186delC on exon 1 and nt1085G > A on exon 6. This type of mutation could induce 17OHD because of complete loss of 17 alpha-hydroxylase activities. And her parents and the twin sister were carriers on CYP17A1 gene. In addition, the mutation nt186delC was a novel point mutation and it was not discovered in normal children.</p><p><b>CONCLUSION</b>A new compound heterozygote carrying two different inherited point mutations on CYP17A1 gene was found, and her parents and twin sister were carriers. This is probably the first report in the world of a twin sisters of whom one is a patient with 17OHD and the other is a carrier of CYP17A1 gene mutation.</p>

Effects of China-made recombinant human growth hormone on the treatment of growth hormone deficiency / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the therapeutic effect of China-made recombinant human growth hormone (r-hGH) in children with growth hormone deficiency (GHD) and to investigate the utilities of various biochemical parameters in GHD diagnosis and treatment.</p><p><b>METHODS</b>Our study comprises of 30 normal children and 71 GHD children treated with China-made r-hGH substitution therapy 0.1 IU x kg(-1) x d(-1) for 6 months. Serum insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), bone turnover markers (Ost, ICTP), and anti-growth hormone antibody (GHAb) were detected before and after r-hGH treatment.</p><p><b>RESULTS</b>After the first 3 and 6 months of treatment, growth velocities of GHD children were significantly increased (13.1 +/- 3.7 and 12.6 +/- 3.6 cm/year) compared with pretreatment values (2.9 +/- 0.8 cm/year, P < 0.01). GHD Children had obviously reduced serum levels of IGF-1, IGFBP-3, and bone turnover markers (Ost, ICTP) compared with normal controls (P < 0.01), and these biochemical parameters improved significantly after treatment (P < 0.01). Growth hormone antibodies were positive in 17 of 45 cases after treatment by binding capacity detection. The binding percentage of growth hormone antibody which was increased more than 30% after the treatment showed a negative correlation with growth velocity (P < 0.01).</p><p><b>CONCLUSIONS</b>(1) The growth stimulating effect and safety were confirmed in using China-made r-hGH in the treatment of GHD children for 6 months. (2) The measurements of serum IGF-1 and IGFBP-3 may serve as useful parameters in the diagnosis of GHD. (3) Serum Ost and ICTP are useful laboratory criteria for evaluating the effect of r-hGH therapy in the early stage. (4) It is necessary to monitor serum levels of GHAb during r-hGH therapy.</p>

Prader-Willi syndrome and genomic imprinting / 中华儿科杂志

<p><b>OBJECTIVE</b>Prader-Willi syndrome (PWS) is an example of a human genetic disorder that involves imprinting genes on the proximal long arm of chromosome 15 and SNRPN gene as a candidate gene for this syndrome. The purpose of this study was to show the molecular genetic defects and genomic imprinting basis in Chinese PWS patients and to evaluate the clinical applications of a differential diagnostic test for PWS.</p><p><b>METHODS</b>Fluorescence in situ hybridization (FISH) and methylation-specific PCR (MSPCR) techniques were applied for 4 clinically suspected PWS patients. Using three probes, including SNRPN probe for identification of the critical locus in PWS region, D15Z1 and PML control probes for identification of the 15p arm and 15q arm, the authors detected the deletions 15q in PWS. MSPCR was based on sodium bisulfite treatment of DNA and PCR primers specific for the maternal and paternal allele.</p><p><b>RESULTS</b>When hybridized with mixed probes, it was found in 2 patients that the central specific signal was absent, but both the flanking control signals were retained, indicating SNRPN gene deletion of chromosome 15q11-13. Bisulfite-modified DNA from all PWS children amplified with methylated allele-specific primer pair showed only maternal 131bp PCR product, indicating the maternal uniparental disomy (UPD15).</p><p><b>CONCLUSION</b>Genomic imprinting plays an important role in the molecular pathogenesis of PWS that caused by paternal microdeletions of 15q11-q13 or maternal UPD of chromosome 15. The basic defect seemed to be an absence of function of PWS genes that are normally expressed only from the paternal chromosome 15. MSPCR is a rapid and simple PCR-based assay compared with other cyto-molecular tests and its results were consistent with the clinical diagnosis of PWS, so it seems to be a reliable diagnostic method for PWS patients who show abnormal methylation at SNRPN. The genetic differential tests for PWS are important in determining familial recurrence risk.</p>