Chromosomal microarray analysis for lateral ventriculomegaly in fetus / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between fetal lateral ventriculomegaly and chromosomal microarray analysis (CMA) abnormalities.</p><p><b>METHODS</b>Fifty fetuses with lateral ventriculomegaly detected by ultrasound and a normal karyotype were included. Forty four fetuses were classified as mild ventriculomegaly (MVM), in which the lateral ventricular atrium was 10-15 mm. Six had severe ventriculomegaly (SVM), with the lateral ventricularatrium being ≥ 15 mm. The fetuses were also divided into isolated (n= 21) and non-isolated groups (n= 29) based on whether they are associated with other anomalies.</p><p><b>RESULTS</b>Thirteen (26%) of the fetuses were found to be abnormal by CMA. For the 44 cases with MVM, 9 (20.9% ) were found to be abnormal, while for the 6 cases with SMV, 4 (66.7%) were found to be abnormal (P>0.05). CMA abnormalities were found in 2 (9.5%) of the 21 fetuses with isolated ventriculomegaly group and 11 (37.9%) of the 29 fetuses with non-isolated ventriculomegaly group (P<0.05).</p><p><b>CONCLUSION</b>Chromosome microdeletions and microduplications are the most common abnormalities found in fetal lateral ventriculomegaly. When ventriculomegaly is associated with other anomalies, the incidence of CMA abnormally is much higher. Prenatal diagnosis is necessary for fetuses with lateral ventriculomegaly.</p>

Prenatal genetic diagnosis of oculocutaneous albinism type II through mutation detection combined with SNPs linkage analysis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To provide prenatal diagnosis for two families affected with oculocutaneous albinism (OCA), in both of which only 1 pathogenic allele has been identified.</p><p><b>METHODS</b>To determine the clinical classification of OCA through DNA sequencing for TYR, P, TYRP1 and SLC45A2 genes in combination with phenotype analysis. Prenatal diagnosis was carried out by direct sequencing and intragenic SNPs family-based linkage analysis.</p><p><b>RESULTS</b>In the first family, only 1 heterozygous mutation c.1255C>T was found in the proband, which was inherited from her mother. Together with its clinical phenotype, the proband was suspected to have OCA2 Screening of amniotic fluid, however, has found no mutation. With family-based linkage analysis, the fetus was deemed to be an OCA2 carrier. In the second family, again only one heterozygous mutation c.1920_1949 del30bp and ins AACA was found in the proband, which was inherited from her father. Together with its clinical phenotype, the proband was suspected to have OCA2. Screening of amniotic fluid has revealed a heterozygous mutation c.1920_1949 del30bp and ins AACA. By family-based linkage analysis, the fetus was deemed to be an OCA2 carrier. Both fetuses had a normal phenotype at birth.</p><p><b>CONCLUSION</b>Prenatal genetic diagnosis has been provided for the first time for two families affected with OCA, in which only 1 pathogenic mutant allele was detected. The combined mutation detection and SNPs linkage analysis has turned out to be successful.</p>

Analysis of OCRL gene mutation in a male infant with Lowe syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify pathological mutation in a Chinese male infant featuring oculocerebrorenal syndrome (also called Lowe syndrome).</p><p><b>METHODS</b>Clinical data of the patient were collected. DNA was extracted from peripheral blood of the infant and his parents. All of the 24 exons and intron-exon splice sites of OCRL gene were amplified with PCR. Mutations were detected by direct sequencing the PCR products.</p><p><b>RESULTS</b>The infant was found to have carried a c.1499G>A (p.R500Q) mutation in exon 15 of the OCRL gene, which was transmitted from his mother, who was heterozygous for the same mutation. The c.1499G>A mutation, discovered in Chinese population for the first time, has been reported to cause severe Lowe syndrome in other ethnic populations.</p><p><b>CONCLUSION</b>The c.1499G>A mutation of the OCRL gene is probably responsible for the disease in the patient. Further study of this mutation may facilitate delineation of the genotype-phenotype correlation of this disease.</p>

A de novo mutation of P gene causes oculocutaneous albinism type 2 with prenatal diagnosis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To determine the genotype of a family affected with oculocutaneous albinism (OCA) and to provide genetic counseling and prenatal diagnosis.</p><p><b>METHODS</b>To determine the genotypes and mutational sites through PCR and sequencing for all exons and exon-intron junctions of 4 OCA genes in the proband and the P gene of her parents. Prenatal genotyping of the fetus was carried out using amniocentesis sample.</p><p><b>RESULTS</b>The patient was diagnosed with OCA2 based on a genotype of c.1327G>A/c.2360C>T. Her father was heterozygous for c.2360C> T, whilst her mother has none of the two mutations. c.1327G>A is therefore a maternal de novo mutation. Neither of the mutations was found in the fetus.</p><p><b>CONCLUSION</b>A maternally inherited de novo mutation c.1327G>A has been identified in the patient. In order to detect de novo mutations, full sequence analysis is necessary.</p>

Prenatal diagnosis of oculocutaneous albinism type II and novel mutations in two Chinese families.

OBJECTIVE: The prenatal genetic diagnosis and counseling of oculocutaneous albinism type II (OCA2) by detecting mutations in the OCA2 gene METHODS: DNA samples were extracted from peripheral whole blood and amniocentesis-derived cells. Polymerase chain reaction and automatic sequence analysis were used to screen the OCA2 gene. RESULTS: Case 1: Two novel heterozygous mutations (p.N476D and p.Y827H) in the P gene were detected in the proband. Molecular prenatal diagnosis on fetal DNA revealed N476D. The pregnancy progressed uneventfully to a normal outcome. Case 2: Mutation analysis of the DNA of family 2 revealed compound heterozygosities for two novel P gene mutations (p.N476D and p.G775R). The pregnant female and the fetus each presented with a single P gene mutation (p.V443I and G775R, respectively). The pregnancy was continued. CONCLUSION: This is the first report of prenatal diagnosis performed in families with oculocutaneous albinism type II (OCA2). Also, this report reveals three novel mutations of the P gene.

Prenatal molecular diagnosis of Duchenne and Becker muscular dystrophy / 北京大学学报(医学版)

Objective: Duchenne and Becker muscular dystrophy (DMD/BMD) is an X-linked lethal recessive disease caused by mutations in the dystrophy gene. There is no efficient treatment for this serious and disabling disease. We established a combination method to detect carriers and perform prenatal diagnosis. Methods: In our study, from 1994 to 2005, using a different combination of 5 methods, including SRY gene amplification, multiplex PCR, multiplex Fluorescence PCR capillary electrophoresis, multiplex ligation-dependent probe amplification (MLPA) and linkage analysis of short tandem repeats (STR), 36 prenatal diagnosis were performed for pregnancies at risk of having a DMD/BMD baby through amniocentesis. Results: Fourteen out of 21 male fetuses were found to be affected and respective pregnancies were terminated. A combined diagnostic rate of 83% was achieved for 30 cases with deletions, duplications, and non-deletion mutations after tested by more than one method. Conclusion: Using a combined method, we can diagnoses patients and carriers in DMD families, and perform prenatal diagnosis for the risk fetus. MLPA provides a simple, rapid and accurate method for deletions and duplications of all the 79 DMD exons. MLPA method for DMD diagnosis is the first report in our country.

A study on the influential factors of G6PD/6PGD specific value assay in the heterozygotes of G6PD gene variants in female patients / 国际检验医学杂志

Objective To improve the detection of G6PD heterozygotes in female patients by the optimum experimental factors of G6PD/6PGD specific value assay.Methods (1)Identifying the mutations of G6PD gene with the use of amplified refractory mutation system (ARMS).(2)Measuring the G6PD/6PGD specific value.Results According to the data analysed by statistics and ROC curve, the optimum experimental factors included that the incubation temperature was 37℃,the substrate concentrations were 0.78 mmol/L G6PNa2 and 0.195mmol/L NADP+, the reaction time was 10min.Conclusion The optimum experimental factors of G6PD/6PGD specific value assay may be used to improve the detection rate of G6PD heterozygotes in female patients.

Study on Na~+-K~+ ATPase and Ca~(2+) -Mg~(2+) ATPase activities of human erythrocyte membrane in G6PD deficient individuals / 中国病理生理杂志

By using Person's separating blood ghost method basically, Na~+-K~+ ATP ase and Ca~(2+)-Mg~(2+) ATPase activties of human erythrocyte membrane were studied. The comparison was made between 11 G6PD deficient subjects and 11 healthy control persons. The results showed that both enzyme activities as well as ouabain inhibition rate were decreased in G6PD deficient individuals (P