Prenatal diagnosis of three fetuses with small supernumerary marker chromosomes / 中华医学遗传学杂志

OBJECTIVE@#To explore the origin and mechanism of small supernumerary marker chromosomes (sSMC) in three fetuses.@*METHODS@#The three fetuses were predicted to have carried chromosomal abnormalities by non-invasive prenatal testing (NIPT). G-banding chromosomal karyotyping analysis were carried out on amniotic fluid samples of the fetuses and peripheral blood samples from their parents. Single nucleotide polymorphism array (SNP-array) was used to determine the origin, size and genetic effect of sSMCs.@*RESULTS@#In fetus 1, SNP array has detected two microduplications respectively at 4p16.3p15.2 (24.7 Mb) and 18p11.32q11.2 (20.5 Mb) which, as verified by fluorescence in situ hybridization (FISH), have derived from a balanced 46,XY,t(4;18)(p15.2q11.2) translocation carried by its father. Fetus 2 has carried a de novo microduplication of 15q11.2-q13.3 (9.7 Mb). The sequence of SMC in fetus 3 has derived from 21q11.2-q21.1 (8.3 Mb), which was inherited from its mother.@*CONCLUSION@#Both NIPT and SNP-array are highly accurate for the detection of sSMC. SNP-array can delineate the origin and size of abnormal chromosomes, which in turn can help with clarification of sSMC-related genotype-phenotype correlation and facilitate prenatal diagnosis and genetic counseling for the family.

Genetic analysis and prenatal diagnosis of a pregnant woman with Sheldon-Hall syndrome / 中华医学遗传学杂志

OBJECTIVE@#To provide genetic testing and prenatal diagnosis for a woman with Sheldon-Hall syndrome.@*METHODS@#The woman was subjected to targeted capture and next-generation sequencing for variant of genes associated with skeletal disorders. And the result was verified in her parents and fetus.@*RESULTS@#The woman was found to harbor a c.188G>A variant of the TNNT3 gene, which was also found in her affected mother and the fetus. Her grandmother and grandmother's brother had similar manifestations, which was in line with an autosomal dominant inheritance. The same variant was not found in her father.@*CONCLUSION@#The c.188G>A variant of the TNNT3 gene probably underlay the distal joint contracture in this pedigree, based on which prenatal diagnosis was attained.

Application value of chromosome microarray analysis for prenatal diagnosis of fetus with ultrasonic abnormalities / 中华医学遗传学杂志

Objective@#To assess the application value of chromosomal microarray analysis (CMA) for prenatal diagnosis of fetus with ultrasound abnormalities.@*Methods@#For 293 fetuses with ultrasound abnormalities (including 168 with structural abnormalities and 125 with non-structured abnormalities) but no common chromosomal abnormalities, CMA assay was performed.@*Results@#Sixteen pathogenic copy number variants (pCNVs) were detected by CMA with a detection rate of 5.46%. The detection rates were 5.95% (10/168) for those with structural abnormalities and 4.80% (6/125) for those with non-structural abnormalities.@*Conclusion@#Compared with conventional karyotyping analysis, CMA can improve the detection of fetal chromosomal abnormality and provide an effective means for prenatal diagnosis.

Genetic analysis of a rare case of Pitt-Hopkins syndrome due to partial deletion of TCF4 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child featuring delayed intellectual development.@*METHODS@#The child and his parents were subjected to conventional G-banding karyotyping and single nucleotide polymorphism array (SNP-array) analysis. Suspected copy number variations (CNVs) were verified in both parents.@*RESULTS@#No karyotypic abnormality was found with the child and his parents. SNP-array results for both parents were normal. The child was found to harbor a de novo 172 kb deletion at 18q21.2 with a physical position of 52 957 042-53 129 237. The deletion only involved one OMIM gene, namely TCF4, resulting in removal of its exons 6 to 8.@*CONCLUSION@#The SNP-array assay has facilitated with the diagnosis of this child. Deletion of 18q21.2 region probably accounts for the Pitt-Hopkins syndrome (PTHS) in this patient.

Application value of chromosome microarray analysis for prenatal diagnosis of fetus with ultrasonic abnormalities / 中华医学遗传学杂志

OBJECTIVE@#To assess the application value of chromosomal microarray analysis (CMA) for prenatal diagnosis of fetus with ultrasound abnormalities.@*METHODS@#For 293 fetuses with ultrasound abnormalities (including 168 with structural abnormalities and 125 with non-structured abnormalities) but no common chromosomal abnormalities, CMA assay was performed.@*RESULTS@#Sixteen pathogenic copy number variants (pCNVs) were detected by CMA with a detection rate of 5.46%. The detection rates were 5.95% (10/168) for those with structural abnormalities and 4.80% (6/125) for those with non-structural abnormalities.@*CONCLUSION@#Compared with conventional karyotyping analysis, CMA can improve the detection of fetal chromosomal abnormality and provide an effective means for prenatal diagnosis.

Identification of a c.1A>G initial codon variation of ARX gene in a child with severe mental retardation / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child featuring severe mental retardation.@*METHODS@#The child was subjected to target region capture and next generation sequencing. Suspected variants were verified by Sanger sequencing.@*RESULTS@#The child was found to harbor a hemizygous c.1A>G (pMet1?) variation of the ARX gene, for which his mother was a heterozygous carrier. The mutation was unreported previously and was predicted to be "probably pathogenic" by bioinformatic analysis.@*CONCLUSION@#The c.1A>G (pMet1?) variant of the ARX gene may underlie the occurrence of severe mental retardation in this child.

Genetic analysis and prenatal diagnosis for a pedigree affected with X-linked Norrie disease / 中华医学遗传学杂志

OBJECTIVE@#To detect mutation of NDP gene in a pedigree affected with Norrie disease.@*METHODS@#Sanger sequencing was used to analyze the NDP gene at Xp11.3. Prenatal diagnosis was performed on amniotic fluid sample after the causative gene was detected.@*RESULTS@#Sanger sequencing has revealed a c.2T>C (p.M1T) missense mutation of the NDP gene in the proband and the fetus. The same variation was not found in ClinVar and HGMD database.@*CONCLUSION@#The c.2T>C mutation of the NDP gene probably underlies the Norrie disease in this pedigree.

Analysis of SYNE1 gene variant in an infant featuring epilepsy and developmental disorders / 中华医学遗传学杂志

Objective@#To explore the clinical features and molecular basis for a child featuring infantile epilepsy and developmental disorders.@*Methods@#Clinical data and peripheral blood samples of the child and his parents were collected. The coding regions of genes associated with nervous system development were subjected to target region capture sequencing.@*Results@#The child developed generalized spasm at 3 months and was diagnosed with epilepsy at 6 months of age. He was treated with Depakin but was diagnosed with mental retardation and developmental retardation at 3 years of age. A novel heterozygous c. 3842T>G variant of the SYNE1 gene was detected. His father was found to carry the same variant and had a history of convulsions in infancy but with no mental or developmental anomalies.@*Conclusion@#A novel variant of SYNE1 gene was identified in this child, and the prognosis may be poor.

Prenatal diagnosis of a case with Branchi-oto-renal syndrome / 中华医学遗传学杂志

Objective@#To carry out prenatal diagnosis for a women with Branchio-oto-renal syndrome by using chromosomal microarray analysis (CMA).@*Methods@#Peripheral blood chromosomal karyotyping and CMA were used to analyze the gravida with an abnormal phenotype. Pathological copy number variants (CNVs) were validated in other members of the family members and her fetus.@*Results@#The gravida and her daughter both had Branchio-oto-renal syndrome and a 8q13.3 microdeletion encompassing the EYA1 gene. The same microdeletion was also found in the fetus. No phenotypic or genotypic anomaly was found with other members of the family.@*Conclusion@#Mutation of the EYA1 gene probably underlies the Branchio-oto-renal syndrome in this family, which is consistent with an autosomal dominant inheritance.

Analysis of SYNE1 gene variant in an infant featuring epilepsy and developmental disorders / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and molecular basis for a child featuring infantile epilepsy and developmental disorders.@*METHODS@#Clinical data and peripheral blood samples of the child and his parents were collected. The coding regions of genes associated with nervous system development were subjected to target region capture sequencing.@*RESULTS@#The child developed generalized spasm at 3 months and was diagnosed with epilepsy at 6 months of age. He was treated with Depakin but was diagnosed with mental retardation and developmental retardation at 3 years of age. A novel heterozygous c.3842T to G variant of the SYNE1 gene was detected. His father was found to carry the same variant and had a history of convulsions in infancy but with no mental or developmental anomalies.@*CONCLUSION@#A novel variant of SYNE1 gene was identified in this child, and the prognosis may be poor.

Prenatal diagnosis of a case with Branchi-oto-renal syndrome / 中华医学遗传学杂志

OBJECTIVE@#To carry out prenatal diagnosis for a women with Branchio-oto-renal syndrome by using chromosomal microarray analysis (CMA).@*METHODS@#Peripheral blood chromosomal karyotyping and CMA were used to analyze the gravida with an abnormal phenotype. Pathological copy number variants (CNVs) were validated in other members of the family members and her fetus.@*RESULTS@#The gravida and her daughter both had Branchio-oto-renal syndrome and a 8q13.3 microdeletion encompassing the EYA1 gene. The same microdeletion was also found in the fetus. No phenotypic or genotypic anomaly was found with other members of the family.@*CONCLUSION@#Mutation of the EYA1 gene probably underlies the Branchio-oto-renal syndrome in this family, which is consistent with an autosomal dominant inheritance.

Prenatal diagnosis of a fetus with 5p15.33 microdeletion / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To screen for genomic copy number variants (CNVs) in a fetus with one sibling affected with Prader-Willi syndrome using single nucleotide polymorphism (SNP) array.</p><p><b>METHODS</b>The fetus and its parents were subjected to chromosomal karyotyping and SNP array analysis.</p><p><b>RESULTS</b>A 5p15.33 microdeletions was identified in the fetus and its phenotypically normal mother with a size of 344 kb (113 576 to 457 213). The father was normal for both testing. Analysis of literature and CNVs database indicated the above CNV to be variant of unclear significance. The couple decided to continue with the pregnancy and gave birth to a healthy boy at full-term. No abnormalities were found during the follow-up.</p><p><b>CONCLUSION</b>This study may provide further data for the phenotype-genotype correlation of 5p15.33 microdeletion, which differs from Cri du Chat syndrome.</p>

Genetic analysis of two cases with Dandy-Walker deformed fetus / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the genetic etiology of two fetuses with Dandy-Walker malformation using single nucleotide polymorphism microarray (SNP-array).</p><p><b>METHODS</b>The fetuses and their parents were subjected to G banding karyotype analysis. The fetuses were also subjected to SNP-array analysis.</p><p><b>RESULTS</b>The parents of both fetuses showed a normal karyotype. One fetus has a 46,X,?i(X)(q10), while for another conventional cell culture has failed. SNP-array showed that one fetus carried a 6p25.3p25.2 microdeletion, and another carried a Xp22.33p22.2 deletion and a Yq11.221q11 duplication. The abnormal fragments have involved FOXC1, SHOX and STS genes, which are associated with Dandy-Walker malformation.</p><p><b>CONCLUSION</b>Alteration of 6p25.3p25.2, Xp22.33p22.2 copy numbers probably underlies the Dandy-Walker syndrome in the fetuses. The disorder may be attributed to abnormal expression of FOXC1, SHOX, and STS genes. SNP-array can provide an important supplement for prenatal diagnosis.</p>

Prenatal genetic analysis of a fetus with Wolf-Hirschhorn syndrome and Edward syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To screen for genomic copy number variants (CNVs) in a fetus with cardiac abnormalities and intrauterine growth retardation through single nucleotide polymorphism microarray (SNP array) and karyotyping analysis.</p><p><b>METHODS</b>The fetus and its parents were subjected to conventional G banding and SNP-array analysis. The results were confirmed with fluorescence in situ hybridization (FISH).</p><p><b>RESULTS</b>G-banding analysis showed that the fetus has a karyotype of 47,XX,+mar. The father has a karyotype of 46,XY,t(4;18) (p15.2q11.2), while the mother showed a normal karyotype. SNP-array detected two microduplications at 18p11.32q11.2 (20.5 Mb) and 4p16.3p15.2 (24.7 Mb) in the fetus. The supernumerary marker chromosome carried by the fetus has derived from the balanced translocation carried by its father. The result was confirmed by FISH.</p><p><b>CONCLUSION</b>Based on the two microduplications, the fetus was diagnosed as Wolf-Hirschhorn syndrome in conjunction with Edward syndrome. Verification of the origin of the supernumerary marker chromosome by SNP-array has provided a basis for prenatal genetic diagnosis.</p>

Analysis on effects of the neonatal hearing screening combined with deafness genes screening in Huzhou / 中国耳鼻咽喉头颈外科

OBJECTIVETo explore the clinical value of the neonatal hearing combined with deafness gene screening.METHODSFrom February 2014 to August 2015, 1933 newborns were included in the study. We analyzed the effects of combined screening of hearing and deafness gene.RESULTSAmong all the 1933 neonates, 71.34% (1379/1933) passed and 28.66% (554/1933) failed the initial hearing screening.The hearing impairment rate was 4.14‰ (8/1933). Genetic screening mutation rate was counted. GJB2 mutation rate was 28.97‰ (56/1933). SLC26A4 mutation rate was 13.97‰ (27/1933). GJB3 mutation rate was 6.21‰ (12/1933). Mitochondrial 12 S rRNA gene mutation rate was 1.03‰ (2/1933). 1 case of 235 delc homozygous mutation did not pass the initial hearing screening and lost to follow-up rescreening. 2 cases of 12 S rRNA 1555A>G homogeneous mutations passed early hearing screening. 8 cases of auditory handicaps were all normal.CONCLUSIONDeafness gene screening can make up for the deficiencies of the universal newborn hearing screening. Joint use of both of them should complement each other and play the biggest role.