Analysis of genetic variant in a fetus featuring pontocerebellar hypoplasia type 6 / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a fetus with cerebellar dysplasia and widened lateral ventricles.@*METHODS@#The couple have elected induced abortion after careful counseling. Skin tissue sample from the abortus and peripheral venous blood samples from both parents were collected for the extraction of genomic DNA, which was then subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing.@*RESULTS@#Prenatal ultrasonography showed increased nuchal translucency (0.4 cm) and widened lateral ventricles. Magnetic resonance imaging revealed infratentorial brain dysplasia. By DNA sequencing, the fetus was found to carry compound heterozygous variants c.1A>G and c.1564G>A of the RARS2 gene, which were inherited from its father and mother, respectively. Among these, c.1A>G was known to be pathogenic, but the pathogenicity of c.1564G>A was unreported previously. Based on the American College of Medical Genetics and Genomics guidelines, the c.1564G>A variant of RARS2 gene was predicted to be likely pathogenic(PM2+PM3+PP3+PP4).@*CONCLUSION@#The compound heterozygous variants c.1A>G and c.1564G>A of RARS2 gene contributed to the fetus suffering from pontocerebellar hypoplasia type 6, which expanded variant spectrum of RARS2 gene.

Identification of a Tp63 gene variant in an abortus with Ectrodactyly, Ectodermal dysplasia, Cleft lip/palate syndrome by whole-exome sequencing / 中华医学遗传学杂志

OBJECTIVE@#To detect potential variant in a male fetus suspected for Ectrodactyly, Ectodermal dysplasia, Cleft lip/palate (EEC) syndrome.@*METHODS@#Peripheral blood samples of the fetus and his parents were collected for the extraction of DNA. Whole-exome sequencing was carried out to detect potential variants. Suspected variants were verified by Sanger sequencing.@*RESULTS@#The fetus was found to carry a heterozygous c.673C>T missense variant of the Tp63 gene, which was known to underlie split-hand/split-foot malformation. The same variant was not found in either parents.@*CONCLUSION@#The heterozygous c.673C>T missense variant of the Tp63 gene probably underlies the EEC syndrome in the fetus. Above finding also expanded the phenotypic spectrum for this variant.

Genomic analysis of Sheldrake origin goose hemorrhagic polyomavirus, China

Goose hemorrhagic polyomavirus (GHPV) is not a naturally occurring infection in geese in China; however, GHPV infection has been identified in Pekin ducks, a domestic duck species. Herein, we investigated the prevalence of GHPV in five domestic duck species (Liancheng white ducks, Putian black ducks, Shan Sheldrake, Shaoxing duck, and Jinyun Sheldrake) in China. We determined that the Jinyun Sheldrake duck species could be infected by GHPV with no clinical signs, whereas no infection was identified in the other four duck species. We sequenced the complete genome of the Jinyun Sheldrake origin GHPV. Genomic data comparison suggested that GHPVs share a conserved genomic structure, regardless of the host (duck or geese) or region (Asia or Europe). Jinyun Sheldrake origin GHPV genomic characterization and epidemiological studies will increase our understanding of potential heterologous reservoirs of GHPV.

Analysis of clinical manifestation and genetic mutations in two patients with Cornelia de Lange syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect potential mutations in two neonates suspected for Cornelia de Lange syndrome (CdLS).</p><p><b>METHODS</b>Peripheral blood samples from the neonates and their parents were collected and analyzed for CdLS-related genes using targeted sequence capture and next-generation sequencing. Suspected mutations were confirmed by direct Sanger sequencing.</p><p><b>RESULTS</b>The neonates were found to respectively carry mutations c.7219C to T and p.D2339Lfs*4 of the NIPBL gene, among which the p.D2339Lfs*4 mutation has not been reported previously. No pathogenic mutation was found in other CdLS-related genes including NIPBL, SMC1A, SMC3, RAD21 and HDAC8.</p><p><b>CONCLUSION</b>The c.7219C to T and p.D2339Lfs*4 mutations of the NIPBL gene probably account for the disease in both patients.</p>

Analysis of PHEX gene mutations in three pedigrees affected with hypophosphatemic rickets / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the molecular basis for three pedigrees affected with hypophosphatemia vitamin D resistant rickets (X-linked hypophosphatemia, XLH).</p><p><b>METHODS</b>Peripheral blood samples from the three pedigrees were collected. Following DNA extraction, the 11 exons and flanking regions of the PHEX gene were subjected to PCR amplification and direct sequencing. Pathogenicity of identified mutations was evaluated through genotype-phenotype correlation.</p><p><b>RESULTS</b>For pedigrees 1 and 2, pathogenic mutations were respectively identified in exon 8 (c.871C>T, p.R291X) and exon 15 (c.1601C>T, p.P534L) of the PHEX gene. For pedigree 3, a novel mutation (c.1234delA, p.S412Vfs*12) was found in exon 11 of the PHEX gene, which caused shift the reading frame and premature termination of protein translation.</p><p><b>CONCLUSION</b>The three mutations probably account for the XLH in the affected pedigrees. The discovery of novel mutations has enriched the spectrum of PHEX gene mutations.</p>

Detection of a patient with ring chromosome 15 by low-coverage massively parallel copy number variation sequencing / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the genetic cause for a child with developmental delay.</p><p><b>METHODS</b>The karotypes of the child and her parents were analyzed with G-banding analysis. Their genome DNA was analyzed with low-coverage massively parallel copy number variation sequencing (CNV-seq) and verified by single nucleotide polymorphism array (SNP-array).</p><p><b>RESULTS</b>The karyotype of the child was ascertained as 46,XX,r(15)(p13q26.3), while both parents showed a normal karyotype. CNV-seq and SNP-array have identified a de novo 15q26.2-q26.3 deletion in the child with a size of approximately 3.60 Mb.</p><p><b>CONCLUSION</b>The abnormal phenotype of the patient carrying the ring chromosome 15 may be attributed to the presence of the 15q26.2-q26.3 microdeletion. The deletion and haploinsufficiency of the IGF1R gene probably underlie the main clinical features of the patient.</p>

Genetic analysis of a mental retardation patient with a rare karyotype involving complex rearrangements of five chromosomes / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the genetic cause of a female patient with severe mental retardation and a history of adverse pregnancy.</p><p><b>METHODS</b>The patient was subjected to G-banded chromosome analysis and single nucleotide polymorphism array (SNP-array) assaying. The correlation between genomic variations and the phenotype was explored.</p><p><b>RESULTS</b>The patient was found to have a complex chromosome rearrangement involving 5 chromosomes. The karyotypes of her parents were both normal. SNP-array assay has identified a 1.6 Mb microdeletion at chromosome 15q21.3 which involved 15 RefSeq genes and a 0.5 Mb microdeletion at 5q21.1 which involved one RefSeq gene.</p><p><b>CONCLUSION</b>The microdeletions, which involved TCF12, ADMA10 and AQP9 genes, probably underlie the mental retardation shown by the patient.</p>

The analysis of common mutation in deafness-associated gene in 111 neonates who failed to pass newborn hearing screening / 临床儿科杂志

Objective To explore the genetic mutation in neonates who failed to pass hearing screening.Methods A total of 111 cases of neonates who failed to pass hearing screening and were conifrmed sensorineural deafness by auditory brainstem evoked potential (ABR) were randomly selected. The heel blood was collected and DNA was extracted.GJB2, SLC26A4, and 11 mutation hotspots in mitochondria gene12SrRNA were tested. The relationship between degree of hearing loss and gene mutation was analyzed.Results In 111 neonates, mutation in deafness gene were found in 24 cases (21.6%) . Among them 14 cases (12.6%) hadGJB2 gene mutation including 5 cases of 235delC single heterozygous mutation, 5 cases of 235delC, and 1 case each of 299_300delAT compound heterozygous mutation, 235delC homozygous mutation, 299_300delAT single heterozygous mutation, 176_191del16 and 235delC compound heterozygous mutation, and 299_300delAT and 508_511dupAACG compound heterozygous mutation respectively. Ten cases (9.0%) hadSLC26A4 gene mutation including 2 cases of IVS7-2A>G single heterozygous mutation, 3 cases of 1226G>A single heterozygous mutation, 2 cases of 2168A>G single heterozygous mutation, and 3 cases of IVS7-2A>G and 2168A>G compound heterozygous mutation. Mitochondrial gene mutations were not detected. Conclusions Deafness gene mutation is detected in more than 1/5 neonates who failed to pass newborn hearing screening. GJB2 gene mutation is the most commons. The implementation of hotspots deafness gene detection can improve the diagnostic rate of deafness.

Phenotypic and genetic analysis of a child featuring multiple malformations due to chromosome 18p deletion / 中华医学遗传学杂志

OBJECTIVE To analyze a neonate with multiple malformations and to correlate its genotype with phenotype. METHODS The karotypes of the child and her parents were subjected to G-banding chromosome analysis, and array comparative genomic hybridization (array-CGH) was used for fine mapping of the aberrant region. RESULTS The karyotype of the child was ascertained as 46,XX,del(18)(p11.2). Array CGH has identified a 9.8 Mb deletion at 18p11.32-p11.22. The patient has presented features such as holoprosencephaly, choanal atresia, heart defect, and craniofacial dysmorphisms. CONCLUSION The de novo 18p deletion probably underlies the main clinical manifestations of the child.

Epidemiological Investigation and Genome Analysis of Duck Circovirus in Southern China / 中国病毒学·英文版

Duck circovirus(DuCV),a potential immunosuppressive virus,was investigated in Southern China from March 2006 to December 2009 by using a polymerase chain reaction(PCR)based method. In this study,a total of 138 sick or dead duck samples from 18 different farms were examined with an average DuCV infection rate of～35%. It was found that ducks between the ages of 40～60 days were more susceptible to DuCV. There was no evidence showing that the DuCV virus was capable of vertical transmission. Farms with positive PCR results exhibited no regularly apparent clinical abnormalities such as feathering disorders,growth retardation or lower-than-average weight. The complete genomes of 9. strains from Fujian Province and 1 from Zhejiang Province were sequenced and analyzed. The 10 DuCV genomes,compared with others genomes downloaded from GenBank,ranged in size from 1988 to 1996 base pairs,with sequence identities ranging from 83.2% to 99.8%. Phylogenetic analysis based on genome sequences demonstrated that DuCVs can be divided into two distinct genetic genotypes,Group I(the Euro-USA lineage)and Group II(the Taiwan lineage),with approximately 10.0% genetic difference between the two types. Molecular epidemiological data suggest there is no obvious difference among DuCV strains isolated from different geographic locations or different species,including Duck,Muscovy duck,Mule duck,Cheery duck,Mulard duck and Pekin duck.