Development and application of a method for molecular diagnosis of 21-hydroxylase deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To develop a method for elucidating genetic basis of 21-hydroxylase deficiency.</p><p><b>METHODS</b>Sanger sequencing of entire 21-hydroxylase coding gene CYP21A2 was carried out to detect point mutations, and multiplex ligation-dependent probe amplification (MLPA) and locus-specific PCR/enzyme restriction method were used to detect large deletions and conversion mutations.</p><p><b>RESULTS</b>Nine children were analyzed. Point mutations of the CYP21A2 gene have been identified as: IVS2 13A/C>G (9 alleles), p.Arg356Trp (1 allele), Cluster E6 (1 allele), p.Gln318X (1 allele), and Prom conv (1 allele). While the former 4 mutations are pathogenic, the role of Prom conv mutation in the pathogenesis was uncertain. Three cases had entire CYP21A2 gene deletions (3 alleles), three had CYP21A1P/CYP21A2 chimeric mutations (3 alleles). The genotypes of all patients were determined. And all of the mutations were inherited from parents.</p><p><b>CONCLUSION</b>A rational method for detecting point mutations and large deletions/conversions of CYP21A2 gene has been established.</p>

Mutational spectrum of phenylalanine hydroxylase gene and identification of novel mutations in patients with hyperphenylalaninemia in Jiangsu province / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the characteristics of phenylalanine hydroxylase (PAH) gene mutations in patients with hyperphenylalaninemia from Jiangsu province by DNA sequencing, and to analyze the spectrum of PAH gene mutations.</p><p><b>METHODS</b>A total of 70 patients and their parents were included in this study. All of the 13 exons and flanking introns of the PAH gene were analyzed with DNA sequencing.</p><p><b>RESULTS</b>Forty five types of mutations were identified, which included 4 novel mutations (L37P, H107R, Q267L, S391T). A total of 125 mutations were identified in 140 alleles (89.3%). All mutations were detected in exons 2-3, 5-7, 9-12 and introns 2, 4, 7 and 8. Most mutations were found in exons 6, 7 and 12. EX6-96A > G, R243Q and R241C were the most common mutations.</p><p><b>CONCLUSION</b>The mutational spectrum of Jiangsu province seems to be different from other regions. The spectrum can offer reliable information for genetic diagnosis of patients with hyperphenylalaninemia.</p>