Genetic study of a trisomy 13 fetus with a false-negative karyotype by chorionic villi analysis / 中华医学遗传学杂志

OBJECTIVE@#To explore the mechanism of a false-negative result from karyotyping of chorionic villi cells for a trisomy 13 fetus featuring multiple malformations.@*METHODS@#For a fetus with multiple malformations by ultrasonography and a 46,XY karyotype by chorionic villi analysis, amniocytes were further analyzed with quantitative fluorescence PCR (QF-PCR), G-banded karyotyping and chromosomal microarray analysis (CMA). Meanwhile, non-invasive prenatal testing (NIPT) was conducted on peripheral blood sample from the pregnant woman to determine the chromosomal composition of cytotrophoblast. After induction of labor, common aneuploidies in placenta and fetal tissue were also analyzed by QF-PCR.@*RESULTS@#QF-PCR, chromosomal karyotyping and CMA analysis of the amniocytes all suggested complete trisomy 13 (47,XY,+13) in the fetus. NIPT also suggested existence of fetal trisomy 13. QF-PCR analysis of the placenta and fetal tissues revealed that cells derived from the maternal surface and right side of fetal surface harbored mosaic trisomy 13, while those derived from other sites of fetal surface of the placenta, umbilical cord, amniotic membrane and fetal muscle tissue harbored trisomy 13.@*CONCLUSION@#Karyotyping of long-term cultured chorionic villus sample may give rise to false negative results due to placental mosaicism. To ensure accurate prenatal diagnosis, discordance between karyotyping of chorionic villi cells, fetal ultrasound and NIPT result should be verified by amniocentesis or cordocentesis and application of multiple cytogenetic and molecular techniques.

Analysis of SLC25A13 gene mutations and prenatal diagnosis for 20 families affected with citrin deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect mutations of SLC25A13 gene in 20 families affected with citrin deficiency and provide prenatal diagnosis for them.</p><p><b>METHODS</b>The 20 probands and their parents were subjected to high-frequency mutation screening combined with Sanger sequencing. After confirming the genotype of each pedigree, genetic counseling and prenatal diagnosis were performed for their subsequent pregnancies.</p><p><b>RESULTS</b>Biallelic pathogenic mutations of the SLC25A13 gene were identified in all probands. These included three deletions (c.851del4, c.1092_1095delT, and c.495delA), two splice-site mutations (IVS6+5G to A and IVS11+1G to A), two nonsense mutations (c.775C to T (p.Q259X) and c.72T to A (p.Y24X)), one duplication mutation (c.1638_1660dup), one insertion (IVSl6ins3kb), and one missense mutation (c.1775A to C (p.Q592P)). Among 24 fetuses undergoing prenatal diagnosis, 8 had normal genotypes, 11 were mutation carriers, while 5 harbored biallelic mutations. Those with wild type alleles or heterozygous SLC25A13 mutations were delivered. Two fetuses harboring homozygous c.851del4 mutations were also delivered. Three fetuses harboring biallelic mutations were terminated.</p><p><b>CONCLUSION</b>Analysis of SLC25A13 gene mutations in families affected by citrin deficiency can provide evidence for molecular diagnosis and facilitate genetic counseling and prenatal diagnosis for the subsequent pregnancy, which can effectively reduce the risk of birth of further affected children.</p>

Genotype and phenotype analysis of a child with partial 18q deletion syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the genotype-phenotype correlation of a child with chromosome 18q deletion syndrome.</p><p><b>METHODS</b>G-banded karyotyping, single nucleotide polymorphism array (SNP array) and fluorescence in situ hybridization (FISH) were performed on the child with abnormal phenotypes. Genotype-phenotype correlation was explored following accurate mapping of the breakpoints on chromosome 18q. SNP array was also performed on the genome DNA derived from peripheral venous blood samples from both parents.</p><p><b>RESULTS</b>Chromosomal analysis revealed that the child has a karyotype of 46, XY, del(18) (q23). SNP array analysis detected a 9.855 Mb deletion (chr18: 68 158 880-78 014 123) at 18q22.2q23. Mapping of the breakpoints suggested that the deletion has overlapped with that of distal chromosome 18q deletion syndrome and encompassed several critical regions for this syndrome. SNP array performed on parental samples suggested that the 18q22.2q23 deletion was de novo in origin. FISH analysis of peripheral blood sample from the child confirmed the presence of 18qter deletion.</p><p><b>CONCLUSION</b>The phenotype of this child may be attributed to the deletion of distal 18q22.2q23, which has encompassed several critical regions for the 18q deletion syndrome.</p>