Characteristics of gene variants among patients with hyperphenylalaninemia from Quanzhou region of Fujian province / 中华医学遗传学杂志

Objective@#To explore the spectrum of genetic variants among patients with hyperphenylalaninemia (HPA) from Quanzhou area of Fujian province.@*Methods@#For 63 children affected with HPA, next generation sequencing was used to identify potential variants in PAH, PTS, PCBD1, QDPR, SPR and GCH1 genes.@*Results@#Fifty two variants underlying phenylalanine hydroxylase deficiency (PAHD) and 13 variants underlying 6-pyruvoyl tetrahydropterin synthase deficiency (PTPSD) were identified. Two patients carried variants of both PAH and PTS genes. The most common variants of the PAH gene were R53H (21.69%), R241C (18.07%), R243Q (12.05%) and EX6-96A>G (7.23%), which were mainly located in exons 7 (32.53%), 2 (21.69%), 6 (9.64%) and 12 (9.64%). The L227M variant of the PAH gene was unreported previously. N52S (35.00%), P87S (25.00%), IVS1-291A>G (10.00%) and T67M (10.00%) variants were the most common variants for the PTS gene and were mainly located in exons 2 (35.00%) and 5 (35.00%).@*Conclusion@#The variant spectrum underlying HPA in Quanzhou area showed a geographical specificity. A novel variant of the PAH gene (L227M) has been detected.

Characteristics of gene variants among patients with hyperphenylalaninemia from Quanzhou region of Fujian province / 中华医学遗传学杂志

OBJECTIVE@#To explore the spectrum of genetic variants among patients with hyperphenylalaninemia (HPA) from Quanzhou area of Fujian province.@*METHODS@#For 63 children affected with HPA, next generation sequencing was used to identify potential variants in PAH, PTS, PCBD1, QDPR, SPR and GCH1 genes.@*RESULTS@#Fifty two variants underlying phenylalanine hydroxylase deficiency (PAHD) and 13 variants underlying 6-pyruvoyl tetrahydropterin synthase deficiency (PTPSD) were identified. Two patients carried variants of both PAH and PTS genes. The most common variants of the PAH gene were R53H (21.69%), R241C(18.07%), R243Q(12.05%) and EX6-96A to G (7.23%), which were mainly located in exons 7 (32.53%), 2 (21.69%), 6 (9.64%) and 12 (9.64%). The L227M variant of the PAH gene was unreported previously. N52S (35.00%), P87S (25.00%), IVS1-291A to G (10.00%) and T67M (10.00%) variants were the most common variants for the PTS gene and were mainly located in exons 2 (35.00%) and 5 (35.00%).@*CONCLUSION@#The variant spectrum underlying HPA in Quanzhou area showed a geographical specificity. A novel variant of the PAH gene (L227M) has been detected.

Mutational analysis of SLC22A5 gene in eight patients with systemic primary carnitine deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the mutations of SLC22A5 gene in patients with systemic primary carnitine deficiency (CDSP).</p><p><b>METHODS</b>High liquid chromatography tandem mass spectrometry (HPLC/MS/MS) was applied to screen congenital genetic metabolic disease and eight patients with CDSP were diagnosed among 77 511 samples. The SLC22A5 gene mutation was detected using massarray technology and sanger sequencing. Using SIFT and PolyPhen-2 to predict the function of protein for novel variations.</p><p><b>RESULTS</b>Total detection rate of gene mutation is 100% in the eight patients with CDSP. Seven patients had compound heterozygous mutations and one patient had homozygous mutations. Six different mutations were identified, including one nonsense mutation [c.760C>T(p.R254X)] and five missense mutations[c.51C>G(p.F17L), c.250T>A(p.Y84N), c.1195C>T(p.R399W), c.1196G>A(p.R399Q), c.1400C>G(p.S467C)]. The c.250T>A(p.Y84N) was a novel variation, the novel variation was predicted to have affected protein structure and function. The c.760C>T (p.R254X)was the most frequently seen mutation, which was followed by the c.1400C>G(p.S467C).</p><p><b>CONCLUSION</b>This study confirmed the diagnosis of eight patients with CDSP on the gene level. Six mutations were found in the SLC22A5 gene, including one novel mutation which expanded the mutational spectrum of the SLC22A5 gene.</p>