Analysis of pathogenic gene variant in a patient with neonatal Donohue syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a newborn infant suspected with Donohue syndrome.@*METHODS@#Whole exome sequencing (WES) was used to screen potential variants in the child. Suspected variants were validated through Sanger sequencing and real-time PCR.@*RESULTS@#The child was found to carry two heterozygous variants in the INSR gene, including c.3258+4(IVS17)A>G and deletion of exon 2, which were respectively inherited from her mother and father.@*CONCLUSION@#The compound heterozygous variants of the INSR gene probably underlie the disease in this patient.

Xp11.22 microduplication related mental retardation: A family report and review of the literature / 中国综合临床

Objective:Xp11.22 microduplication syndrome is a very rare disease.In July 2017, 2 male patients with Xp11.22 microduplication syndrome of the same family were admitted to the 980th Hospital of the PLA Joint Service Support Force.Diagnosis process: the medical exons of the proband and his parents were sequenced by high-throughput sequencing technology, and the gene sequences were compared and analyzed.Genomic copy number variation of proband, his uncle and his mother were analyzed by chromosome microarray.Medical exon sequencing did not find gene mutations that were highly correlated with the clinical phenotype of the proband.The results of chromosome microarray analysis showed that the proband had a 629 kb fragment duplication in the chrXp11.22 region, and the gene locus was Xp11.22 (53, 188, 779-53, 817, 598), which contained HSD17B10, HUWE1, SMC1A, KDM5C and IQSEC2 important OMIM genes, associated with Xp11.22 microduplication syndrome, it was a pathogenic copy number change.The same 612Kb fragment duplication in the chrXp11.22 region, locus Xp11.22 (53, 188, 779-53, 800, 670) was found in his uncle.And the same 803Kb fragment duplication in the chrXp11.22 region, locus (53, 188, 779-53, 991, 495) was found in his mother.In the families with unknown intelligence, especially male patients, it is necessary to detect the whole genome copy number of the patients to be alert to Xp11.22 microrepeat syndrome.

Clinical and genetic analysis of a patient with tyrosinemia type I but without elevated succinylacetone / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical manifestation and genetic mutation of a child with tyrosinemia type I but without elevated succinylacetone.@*METHODS@#Clinical data of the patient was collected. Tandem mass spectrometry and gas chromatography mass spectrometry were used to analyze the blood amino acid and urine organic acid component of the proband. DNA was extracted from the child and his parents and used for mutation analysis.@*RESULTS@#The proband was of acute type, with features including hepatomegaly, jaundice, anemia and tendency of bleeding. Serum levels of Tyrosine, Methionine and Phenylalanine were 397.12 μmol/L, 896.16 μmol/L and 292.52 μmol/L, respectively, which all distinctly exceeded the normal levels. The level of phenyllactic acid and 4-hydroxyphenyl-lactic acid of proband's urine were 17.4 μmol/L and 417.0 μmol/L, respectively, which also exceeded the normal levels, but the level of succinylacetone was within the normal range. Compound heterozygous mutations of the FAH gene, namely c.634delT (p.L212Wfs*20) and c.455G>A (p.W152X), were detected in the proband, which were both predicted to be pathogenic and were inherited from her father and mother, respectively.@*CONCLUSION@#For children with tyrosinemia type I, detection of urine succinylacetone by gas phase mass spectrometry can be negative. The diagnosis of tyrosinemia type I must rely on genetic testing and/or enzymatic assaying.

Analysis and prenatal diagnosis of PKLR gene mutations in a family with pyruvate kinase deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To evaluate the feasibility of genetic and prenatal diagnosis for a family affected with pyruvate kinase deficiency (PKD).</p><p><b>METHODS</b>Targeted sequence capture and high-throughput sequencing technology was used to detect the exons and exon-intron boundaries of the PKLR gene in a clinically suspected PKD patient. Meanwhile, the genotype of the pedigree was validated by Sanger sequencing. Prenatal genetic diagnosis was performed by amniotic fluid sampling after genotype of the mother of the proband was determined.</p><p><b>RESULTS</b>The proband was found to harbor double heterozygous mutations, c.661G>A (Asp221Asn) and c.1528C>T (Arg510Ter), which resulted in amino acid substitution Asp221Asn and Arg510Ter. Such mutations were confirmed by Sanger sequencing. The mother and father of the proband were detected to have respectively carried c.1528C>T (Arg510Ter) and c.661G>A (Asp221Asn) mutation. The fetus was found to have carried the same mutations as the proband. Following selected abortion, analysis of fetal tissue was consistent with the result of prenatal diagnosis.</p><p><b>CONCLUSION</b>The compound mutations of c.661G>A and c.1528C>T of PKLR gene probably underlie the PKD in the family. Prenatal diagnosis of the mutations analysis can facilitate detection of affected fetus in time.</p>

Effects of Bushen Huoxue Fang on estrogen receptor alpha mRNA in pituitary body of ovariectomized rats with collagen-induced arthritis / 中国组织工程研究

BACKGROUND: Pharmacological researches demonstrate that Chinese crude drugs of invigorating the kidney contain flavonoids such as prepared rhizome of rehmannia and kudzuvine root, they possess phytoestrogenic effect, among them, isoflavone acts as a regulator of estrogen receptor.OBJECTIVE: To approach the effects of self-planned Bushen Huoxue Fang (BSHXF) on the serum estradiol and estrogen receptor α mRNA expression in pituitary gland in rats with collagen-induced arthritis. DESIGN, TIME AND SETTING: Randomized grouping controlled animal experiment was performed in the central laboratory of Bethune Intemational Peace Hospital of Chinese PLA between May 2006 and May 2008. MATERIALS: Sixty female and healthy Wistar rats were randomly divided into sham operated group (n=10) and operation group (n=50). Operation group was reproduced collagen-induced arthritis model at 2 weeks following ovariectomy. The rats of arthritic index ≥ 5 were assigned into model group, BSHXF group, methotrexate (MTX) group, and MTX + BSHXF group, each group included 10 rats. The Chinese crude drugs were bought from LERENTANG drugstore in Shijiazhuang, including rhizoma drynariae, safflower, prepared rhizome of rehmannia, Herba Epimedii, danshen root, kudzuvine root and so on. After routine decoction, centrifugalization, rogue and condensing 1.3 kg/L decoction, the solution was sealed up, divided pack and reserved at 4℃.METHODS: Sham operated group and model group were intragastrically administered with normal saline 2 mL per day; BSHXF group with BSHXF decoction 2 mL per day; MTX group with MTX 2.6 mg/kg (2 mL) once a week, and normal saline 2 mL per day at other time points; MTX + BSHXF group with MTX 2.6 mg/kg (2 mL) once a week and BSHXF juice 2 mL per day. Each group was given 6 weeks.MAIN OUTCOME MEASURES: After blooding by abdominalis aorta, magnetic-split enzyme linked immunosorbent assay was applied to detect the level of serum estradiol. Reverse transcription-polymerase chain reaction detected the expression of estrogen receptor a mRNA in rat pituitary gland.RESULTS: Compared with model group, the expression of estrogen receptor a mRNA in pituitary gland increased in the MTX group, but there was not statistically significant. BSHXF + MTX group showed a significantly increased expression (P < 0.01). The expression of estrogen receptor α mRNA in BSHXF group was higher than MTX group, but lower than BSHXF + MTX group (P < 0.05). No significant difference existed between BSHXF group, BSHXF + MTX group and sham operation group. Compared with sham operation group, there were statistically significant decrease of estradiol in the model group. Compared with model group, the estradiol levels were shown to increase in three treatment groups. Among them, MTX group had slightly slower level with no significant difference (P > 0.05), while BSHXF + MTX group had the most obvious increase, which was close to normal level (P < 0.01). There was a significantly positive correlation between estradiol and the expression of estrogen receptor o mRNA (r=0.483, P < 0.05).CONCLUSION: Serf-planned BSHXF possessing oestrogenic hormonelike role can elevate the level of serum estradiol and upregulate the expression of estrogen receptor a mRNA in pituitary gland.