Genetic testing and pregnancy outcome of 337 fetuses with urinary system anomalies / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis and pregnancy outcome of fetuses with urinary system anomalies.@*METHODS@#Ultrasonographic features, genetic testing and pregnancy outcomes of 337 fetuses with urinary system anomalies identified by prenatal ultrasonograhy were collected for analysis.@*RESULTS@#Ultrasonographic features of the fetuses were mainly characterized by hydronephrosis or hydronephrosis, polycystic kidney disease, and renal dysplasia. Thirty four fetuses (10.1%) were found to harbor a genetic defect, including 14 numerical chromosomal disorders, 10 structural chromosomal aberrations, and 10 pathogenic copy number variations (CNVs). In 31 cases, the parents elected induced labor. For the 303 fetuses with negative findings, 142 were born by spontaneous delivery or Caesarean section, 48 cases underwent induced labor, 1 case had miscarriage, and the remaining 112 cases had unknown or missed pregnancy outcomes.@*CONCLUSION@#Hydronephrosis or hydronephrosis, polycystic kidney disease, and renal dysplasia are the most common findings among fetuses with urinary system anomalies. Approximately 10.1% of such fetuses are positive by genetic testing.

Genome-wide copy number variations analysis in 64 patients with unexplained intellectual disability / 中华实用儿科临床杂志

Objective To investigate the genetic basis of patients with intellectual disability,and to assess the application of single nucleotide polymorphisms (SNP)-array in the molecular diagnosis of intellectual disability.Methods Sixty-four patients with intellectual disability who were identified in Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from January 2013 to June of 2015 were enrolled.Genomic DNA was extracted from peripheral blood and was analyzed with Illumina Humancyto SNP-12 300K gene array chip.All identified copy number variants (CNVs) were analyzed with references from databases such as ClinVar,DECIPHER,OMIM and DGV(Database of Genomic Variants),as well as comprehensive literature review from PubMed database to determine the pathogenicity of CNVs.Results Sixteen cases of the above 64 patients were found to have CNVs with genomic alterations,including 6 cases microdeletions/microduplications associated with known syndromes,3 cases microdeletions and microduplications with clear clinical relevance (non-syndrome),1 case numerical chromosome aberration,1 case unbalanced translocation and 5 cases CNVs of unknown clinical significance.The detection rate was 25% (16/64 cases).Among these 16 abnormalities,6 cases of them could not be detected by using karyotyping analysis because their sizes were less than 5 Mb,and the smallest detected missing fragment was 0.53 Mb.Conclusion SNP-array gene chip technique with the advantages of higher efficiency,high-resolution and good accuracy,which can be applied to the genetic diagnosis of intellectual disability.

Application of SNP-array technology in the genetic analysis of pediatric patients with growth retardation / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the value of single nucleotide polymorphism array (SNP-array) for the analysis of pediatric patients with growth retardation.</p><p><b>METHODS</b>One hundred eighty one children with growth retardation were enrolled. DNA was extracted from peripheral samples from the patients, and whole genome copy number variations (CNVs) were detected using Illumina Human Cyto SNP-12. All identified CNVs were further analyzed with reference to databases including ClinGen, ClinVar, DECIPHER, OMIM and DGV as well as comprehensive review of literature from PubMed to determine their pathogenicity.</p><p><b>RESULTS</b>Forty seven patients (26%) with abnormal CNVs were detected, which included 12 known microdeletions/microduplications syndrome (26%), 10 pathogenic non-syndromic CNVs (21%), 3 numerical chromosome aberrations (6%), 3 unbalanced translocations (6%), 4 pathogenic mosaicisms (9%) and 15 cases with unknown clinical significance (32%). After excluding obvious numerical and/or structural chromosomal abnormalities, this study has detected 15 pathogenic microdeletions/microduplications sized 5 Mb or less, which may be missed by routine chromosomal karyotyping. In addition, there were 3 cases with loss of heterozygoisty (LOH) containing known or predicted imprinting genes as well as 2 cases with suspected parental consanguinity.</p><p><b>CONCLUSION</b>SNP-array technology is a powerful tool for the genetic diagnosis of children with growth disorders with advantages of high resolution and improved accuracy.</p>

Genotypes of 1 571 cases of Hb H disease in Guangxi area / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the status and genotypes of Hb H disease in GuangXi area.</p><p><b>METHODS</b>Human genomic DNA of 50 377 suspected thalassemia patients was extracted from blood, amniotic fluid and chorionic villi by beads. The deletion of α-thalassemia was detected by Gap-PCR, and the gene mutation of α or β-thalassemia was detected by PCR- RDB. Performing multiplex ligationdependent probe amplification detection and gene sequencing in α or β-globin for the specimens in question.</p><p><b>RESULTS</b>There were 1 571 Hb H disease patients in total from 2011 to 2013, and the detection rates were 2.82%, 3.54% and 3.00% respectively. The vast majority of patients had the Southeast Asian deletion (--(SEA)) on one allele. The - α³·⁷ (rightward) deletion was the most common on the other allele, followed by Hb Constant Spring (Hb CS), the -α(4.2) (leftward) deletion, Hb Westmead (Hb WS) and Hb Quong Sze (Hb QS) mutations. There were 33 Hb H disease patients which genotypes was α(CS)α/α (CS)α. Five patients had THAI deletion(--(THAI)) with deletion or point mutation of α-thalassemia. 95 patients had concomitant β-thalassemia (β-thal) heterozygosity. Tere was a novel genotype of --(SEA)/-α²¹·⁹ causing Hb H disease.</p><p><b>CONCLUSION</b>GuangXi area had a high accidence of Hb H disease, the results reflected the genetic diversity and genetic heterogeneity of Hb H disease, the latter may also occur new mutations or combined β-thalassemia, some effective measures should be taken to strengthen screening efforts to prevent underdiagnosis of Hb H disease.</p>

Gene distribution characteristics of deletional α-thalassemia in Guangxi region / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the detection rate and gene distribution characteristic of deletional α-thalassemia in Guangxi area, and to provide theoretic basis for thalassemia gene diagnosis and genetic counseling.</p><p><b>METHODS</b>The regular gene diagnosis of 3 types of α-thal (-- (SEA),- α(3.7),- α(4.2)) was performed by gap-PCR, multiple ligation probe and gene sequencing for globin α or β were used to detect those samples whose genotype and phenotype were not consistent. And the distribution characteristic of α-thalassemia gene in Guangxi area was then analyzed.</p><p><b>RESULTS</b>Out of 51 191 suspected thalassemia patients, there were 19 853 cases of deletional a-thalassemia, accounted for 39.9% in total positive rate, including 19 780 cases of regular types(--(SEA), - α(3.7), - α(4.2)), 61 cases of Thailand-type deletion, 9 cases of triplet type (Hong Kong) (ααα(HK)), 1 case of 21.9 kb deletion type and 2 cases of 809 bp deletion type.</p><p><b>CONCLUSION</b>Types of deletional a-thalassemia were complex and accounted for large proportion in Guangxi area. Special gene diagnoses were needed for those couples whose genotype and phenotype were not consistent, in order to provide reliable basis for genetic counseling and prenatal diagnosis.</p>

Gene array analysis in 56 cases of children with growth retardation / 临床儿科杂志

Objective To investigate the genetic basis of the children with growth retardation. Methods From January to October 2013, the 56 patients with growth retardation were enrolled in this study. Genomic DNA was extracted from peripheral blood and was analyzed with gene array chips. Results Abnormalities were found in 12 patients (6 cases of sex chromosome abnormalities and 6 cases of autosomal aberration) and the detection rate was 21.4%. Four patients had the copy-number variations of smaller than 2.5Mb in size which could not be found by karyotyping analysis. Conclusions SNP-array gene chip could be used in the genetic diagnosis of growth retardation.

Genetic Evolution of Neuraminidase Gene of Influenza A/H1N1 Virus / 中山大学学报(医学科学版)

[Objective]This study was designed to investigate the genetic evolution of the neuraminidase(NA)gene of seasonal A/H1N1 and 2009 novel A/H1N1 inflilenza virus,and discuss the genetic variation of influenza A virus.[Methods]The virus strains were separately isolated from the clinical samples collected in 2006 and 2009,and then identified as seasonal A/H1N1 and novel A/H1N1.The full length of the NA gene of these strains was amplified by RT-PCR.Then the genetic evolution and mutations of important functional sites were analyzed.[Results]The homology of NA gene between the 2009 novel A/H1N1 isolates and 2006 seasonal A/H1N1 isolates was low(77.9%～78.8%),so was the homology of NA gene between the 2009 novel A/H1N1 isolates and representative strains of different periods and 1979-2001 WHO recommended vaccine strains(78.1%～79.3%).But compared with the WHO recommended vaccine strains of 2009 novel A/H1N1,the homology reached more than 99%.The genetic evolution analysis revealed that NA gene of 2009 novel A/H1N1 had the closest genetic relationship with the swine influenza A virus(A/swine/Belgium/1/1983)from Eurasian Iineage,and some of the antigenic sites and neuraminidase active sites of NA gene of seasonal A/H1N1 were mutated after 2005.[Conclusion]The NA gene of 2009 novel A/H1N1 may originate from Eurasian Iineage of swine influenza virus.The variation of NA gene of seasonal A/H1N1 has occurred in a certain degree.Hence,it is very necessary to continuously monitor the variant of influenza A virus.