Case report and literature review of ATP6V0A2 gene mutation features of the patient with congenital cutis laxa / 天津医药

The incidence of autosomal recessive cutis laxa induced by ATP6VOA2 gene mutation is extremely low in neonates and rarely reported in China.There was one case of ATP6VOA2 gene mutations caused autosomal recessive cutis laxa diagnosed in Tianjin Children's Hospital.This article reviewed the diagnosis and treatment of the patient and reviewed the relevant literature,in order to improve the understanding of the disease.

Clinical analysis of 15 851 children at risk of inherited metabolic diseases / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore the value of urine gas chromatography-mass spectrometry (GC-MS) in the screening of children at risk of inherited metabolic diseases (IMD), and to identify the disease spectrum of IMD and the clinical characteristics of children with IMD.</p><p><b>METHODS</b>The clinical data of 15 851 children at risk of IMD who underwent urine GC-MS in the Tianjin Children's Hospital between February 2012 and December 2016 were retrospectively analyzed.</p><p><b>RESULTS</b>In the 15 851 children, 5 793 (36.55%) were detected to have metabolic disorders. A total of 117 (0.74%) children were confirmed to have IMD, including 77 cases of methylmalonic acidemia (65.8%). The clinical manifestations of confirmed cases in the neonatal period mainly included jaundice, metabolic acidosis, abnormal muscular tension, feeding difficulty, poor response, and lethargy or coma. The clinical manifestations of confirmed cases in the non-neonatal period mainly included delayed mental and motor development, metabolic acidosis, convulsion, recurrent vomiting, and anemia.</p><p><b>CONCLUSIONS</b>GC-MS is an effective method for the screening for IMD in children at risk. Methylmalonic acidemia is the most common IMD. The clinical manifestations of IMD are different between the confirmed cases in the neonatal and non-neonatal periods.</p>

Mutation analysis of a family with 2-Methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency / 中华儿科杂志

<p><b>OBJECTIVE</b>The aim of this study was to explore the genetic features of a family with 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency (MHBDD) which may provide the basis for the diagnosis and genetic counseling.</p><p><b>METHOD</b>Clinical data of the proband was collected, total RNA and genomic DNA were extracted from the peripheral blood. The whole coding region of the ACAT1 gene was amplified by RT-PCR. 5' noncoding region of the ACAT1 gene and all 6 exons and flanking intron regions of the HADH2 gene were amplified by PCR. All amplification products were directly sequenced and compared with the reference sequence.</p><p><b>RESULT</b>(1) The patient was a one-year-old boy who presented with psychomotor retardation and astasia when he was admitted to the hospital. Biochemical test revealed slight hyperlactatemia (3.19 mmol/L) and magnetic resonance imaging showed delayed myelination. 2-Methylacetoacetyl-CoA thiolase deficiency was suggested by gas chromatography-mass spectrometry. (2) There was no mutation in the ACAT1 gene and a hemizygous missense mutation c.388C > T was found in the 4 exon of the HADH2 gene which resulted in p. R130C. Proband's mother was the heterozygote and the father was normal.</p><p><b>CONCLUSION</b>This is the first report on MHBDD patient and HADH2 mutation in China. p.R130C is responsible for the pathogenesis of the disease in the infant.</p>

Analysis of ALDH5A1 gene mutation in a Chinese Han family with succinic semialdehyde dehydrogenase deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect potential mutation in ALDH5A1 gene for a family affected with succinic semialdehyde dehydrogenase deficiency diagnosed by clinical inspection and urine screening.</p><p><b>METHODS</b>Polymerase chain reaction and direct DNA sequencing were carried out for the affected child and her parents. Suspected ALDH5A1 gene mutations were verified in 100 healthy controls to exclude polymorphisms.</p><p><b>RESULTS</b>The child was found to have carried 2 heterozygous missense mutations in the coding region of ALDH5A1 gene, namely c.527G>A and c.691G>A, for which her mother and father were respectively heterozygotes. The same mutations were not detected in 100 healthy controls. The child was also found to have carried two previously described polymorphisms including a heterozygous c.545C>T(derived from her father) and a homozygous c.538C>T(derived from her mother).</p><p><b>CONCLUSION</b>Missense mutations of c.527G>A and c.691G>A in the ALDH5A1 gene are responsible for the pathogenesis of the disease in this family.</p>

Correlation between genotypes and biochemical phenotypes of phenylalanine hydroxylase in patients with phenylketonuria / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the correlation between genotypes and biochemical phenotypes of phenylalanine hydroxylase (PAH) in patients with phenylketonuria (PKU).</p><p><b>METHODS</b>Thirteen exons and flanking introns of PAH gene in 102 patients with high blood phenylalanine levels (Phe > 120 umol/L) at initial diagnosis were amplified with polymerase chain reaction and analyzed with single strand conformation polymorphism (SSCP), denaturing high performance liquid chromatography (DHPLC) and DNA sequencing. Correlation between genotypes and biochemical phenotypes was analyzed.</p><p><b>RESULTS</b>Biochemical assaying has indicated that 69 patients had classical PKU (Phe> 1200 umol/L), 31 were moderate (Phe 600-1200 umol/L), and 2 were mild (Phe 400-600 umol/L). More than 41 mutations and 75 genotypes have been identified. There were 9 (8.8%) homozygous mutations, which included 3 cases with R111X/R111X, 1 case with IVS4-1G>A/IVS4-1G>A, 3 cases with R243Q/R243Q and 2 cases with V399V/V399V. Among these 8 belonged to classic PKU phenotypes, except for a R243Q/R243Q genotype which has led to a moderate phenotype. In 91 patients carrying compound PAH mutations, 61 were classic, 29 were moderate, and 1 was mild. Patients who were heterozygous for R111X/R243Q and EX6-96A>G(Y204C)/R243Q were found with both classic and moderate PKU phenotypes. Certain individuals who have carried 2 null mutant alleles such as R111X/V399V, EX6-96A>G/Y356X and EX6-96A>G/V399V only showed a moderate phenotype. Individuals with R111X/A165D and R176X/A165D genotypes, on the other hand, respectively presented moderate and classic PKU phenotypes.</p><p><b>CONCLUSION</b>Ninety percent of our patients are compound heterozygotes. Independent assortment of mutant alleles has resulted in a complex genotype-phenotype correlation. Although in most cases a correlation may be found, caution should still be taken upon genetic counseling. The phenomena where similar or even identical genotype may give rise to different biochemical phenotypes have implied that other factors may also influence the phenylalanine metabolism.</p>

Effects of low-iodine diet on the expression of homeobox gene nkx2.1 in rat cerebral tissue / 中国地方病学杂志

Objective To study the influence of low-iodine diet on the expression of homeobox gene nkx2.1 in rat cerebral tissue. Methods Forty female Wistar rats were randomly divided into two groups according to body. quality: low-iodine group and control group,both fed with low-iodine feed at an iodine content of 13.66 μg/kg,respectively given the deionized water and 200 μg/L KIO3 solution. The hormone levels of two group rats were determined with chemiluminescence immunoassay after three months, and then mated with healthy male rats. Cerebral tissues were taken from the fetus of 16-day pregnancy,newborn and 20 days old offspring in low-iodine and control group to detect the content of nkx2.1 mRNA using real-time fluorescence quantitative PCR (FQ-PCR) techniques. Results Serum TT3, TT4, FT3, FT4 level of rats in low-iodine group(0.89±0.20, 0.32±0.16, 3.33± 0.61, 3.28±0.80) was respectively lower than that in the control group(1.04±0.06, 39.42±14.68,4.83±0.33, 26.99±4.48;t = 2.71,6.52,5.70, 12.89, P < 0.05 or < 0.01). The relative nkx2.1 mRNA expression was(5.60± 0.30)×10-3, (1.20 ± 0.29)×10-3, (0.18± 0.06)×10-3 respectively in the fetus of 16-day pregnancy, newborn and 20 days old offspring of control group, while it was (3.00 ± 0.55)×10-3, (1.90 ± 0.21)×10-3,(0.69 ± 0.15)×10-3 in the low-iodine group. The difference of nkx2.1 mRNA expression was significant among fetal and neonatal rats in the control group and low-iodine group(F = 210.07,162.40, both P < 0.01). The nkx2.1 mRNA expression of newborn rats was lower than that of 16-day pregnancy in both groups(P < 0.01), and that of 20 days old rats was lower than that of 16-day pregnant and neonatal rats(P < 0.01). The 16-day pregnant rats of control group had obviously higher level of nkx2.1 expression than those in the low-iodine group(t = 16.073, P< 0.01), while the nkx2.1 of newborn and 20 days old low-iodine rats expressed much higher than healthy rats(t = 7.573,12.221, P < 0.01). Conclusions Brain development retardation caused by low-iodine is closely related to nkx2.1 differential expression in the brain tissue.