Disease spectrum and pathogenic genes of inherited metabolic disorder in Gansu Province of China / 中国当代儿科杂志

OBJECTIVES@#To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder (IMD) among neonates in Gansu Province of China.@*METHODS@#A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021. A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.@*RESULTS@#A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates, and the overall prevalence rate of IMD was 0.63 (1/1 593), among which phenylketonuria showed the highest prevalence rate of 0.32 (1/3 083), followed by methylmalonic acidemia (0.11, 1/8 959) and tetrahydrobiopterin deficiency (0.06, 1/15 927). In this study, 166 variants were identified in the 28 pathogenic genes, with 13 novel variants found in 9 genes. According to American College of Medical Genetics and Genomics guidelines, 5 novel variants were classified as pathogenic variants, 7 were classified as likely pathogenic variants, and 1 was classified as the variant of uncertain significance.@*CONCLUSIONS@#This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Investigation on the Medical Reference Range of the Normal Neonates with the Amino Acid and Acyl Carnitine Tandem Mass Spectrometry in Gansu Province / 现代检验医学杂志

Objective To establish the medical reference range of amino acid and acyl car-nitine tandem mass spectrometry in normal neonates in Gansu province,and provide the basis for the determination of amino acid and acyl carnitine test results in the screening of neonatal genetic metabolic diseases.Methods A non derivatization tandem mass spectro-metry kit was used to screen 77 957 samples of neonates in Gansu province.Statistical soft ware SPSS19.0 was used to analyze the 95％ reference range of 11 amino acids and 31 kinds of acylcarnitine indexes.Results The medical reference value(μmol/L) of the series mass spectra of newborn genetic metabolic diseases in Gansu province was established:ALA (216.17 ～ 727.58),ARG (1.80～33.03),CIT (4.87～30.67),GLY (183.43～841.46),LEU (79.85～289.45),MET (3.32～25.86),ORN (34.09～225.15),PHE (27.04～83.37),PRO (79.44～337.59),TYR (37.61～177.79),VAL (59.31～250.95),C0 (9.35～45.35),C2 (2.62～25.40),C3 (0.46～3.3),C3DC_C4OH (0.02～0.20),C4 (0.08～0.31),C4DC_C5OH (0.10～0.32),C5 (0.05～0.30),C5:1 (0.00～0.01),C5DC_C6OH (0.04～0.22),C6 (0.01～0.06),C6DC (0.03～0.13),C8 (0.02～0.08),C8:1 (0.05～0.31),C10 (0.02～0.12),C10:1 (0.03～0.10),C10:2 (0.01～0.10),C12 (0.02～0.13),C12:1 (0.02～0.10),C14 (0.07～0.30),C14:1 (0.03～0.13),C14:2 (0.01～0.03),C14OH (0.00～0.02),C16 (0.59～4.91),C16:1 (0.03～0.30),C16:1-OH (0.01～0.08),C16OH (0.01～0.03),C18 (0.29～1.30),C18:1 (0.57～2.32),C18:1-OH (0.01～0.05),C18:2 (0.08～0.51) and C18OH (0.00～0.02).Conclusion The establishment of the medical reference range of the normal neonatal dryblood spot amino acid and acyl carnitine tandem mass spectrometry in Gansu province can provide reference for the determination of the results of the cluster mass spectrometry in this region.

Value of oral mucosa cast-off cells as samples in fluorescent in situ hybridization for the diagnosis of Down's syndrome / 中国当代儿科杂志

<p><b>OBJECTIVE</b>At present, blood and skin biopsy tissues are used in the fluorescent in situ hybridization (FISH) test for the diagnosis of Down's syndrome, however, the samples are usually obtained invasively. This study explores the value of oral mucosa cast-off cells in the FISH test, as samples obtained non-invasively, for the diagnosis of this disorder.</p><p><b>METHODS</b>Peripheral blood and oral mucosa cast-off cells were sampled for the FISH test in 16 children with suspected Down's syndrome between March 2010 and March 2011. Chromosomal karyotype analysis of peripheral blood lymphocytes ("gold standard" for the diagnosis of Down's syndrome) was also conducted.</p><p><b>RESULTS</b>The FISH test, in which both peripheral blood and oral mucosa cast-off cells were examined, showed that 14 children had 21-trosomy syndrome and the other 2 children had normal numbers of cromosome 21. The results of the FISH test were the same as the results of the chromosomal karyotype analysis.</p><p><b>CONCLUSIONS</b>Use of the FISH method to test samples of oral musoca cast-off cells is non-invasive and reliable for the diagnosis of Down's syndrome in children, and is hence worthy of recommendation.</p>

Mutation analysis of KIF21A gene in a Chinese family with congenital fibrosis of the extraocular muscles type I / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To determine the mutation responsible for the congenital fibrosis of the extraocular muscles type I(CFEOM1) in a Chinese family.</p><p><b>METHODS</b>Direct sequencing of exons 20 and 21 in the KIF21A gene was performed for the proband. The mutation c.2860C to T in exon 21 was examined by allele specific-PCR (AS-PCR) analysis in other family members. Haplotype analysis was performed using four STR markers (D12S1668, D12S2194, D12S331 and D12S1048).</p><p><b>RESULTS</b>A heterozygous mutation c.2860C to T in the KIF21A gene was identified in all three affected members with CFEOM1. Haplotype analysis suggested that the mutation might derive from maternal germline mosaicism.</p><p><b>CONCLUSION</b>This Chinese family with CFEOM1 may be caused by a c.2860C to T mutation in the KIF21A gene.</p>

Mutation analysis of the PAH gene in patients with phenylketonuria in Gansu province / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To characterize the mutations of the phenylalanine hydroxylase (PAH) gene in patients with phenylketonuria in Gansu province.</p><p><b>METHODS</b>Mutations of the PAH gene were detected in exons 3, 5, 6, 7, 11 and 12 with flaking introns of PAH gene by PCR and DNA sequencing.</p><p><b>RESULTS</b>Mutations were identified in 45/58 alleles (detection rate: 96.4%), in total of 18 variants. Among them IVS12+5G>C was a novel mutation. The most frequent mutations were R243Q (22.7%), V399V (12.1%), EX6-96A>G (5.2%), R413P (5.2%) and IVS4-1G>A (5.2%), followed by Y356X (3.4%), R111X (3.4%) and INS7+2T>A (3.4%).</p><p><b>CONCLUSION</b>The mutations of the phenylalanine hydroxylase gene in patients with phenylketonuria in Gansu province were similar to that in other areas of China, with obvious difference in mutation rate of some mutations.</p>