Prenatal diagnosis for Walker-Warburg syndrome by whole exome sequencing / 临床检验杂志

Objective To perform prenatal diagnosis for a fetus with hydrocephalus and congenital heart disease by whole exome se-quencing ( WES) , and then provide genetic counseling for the next pregnancy. Methods DNAs from amniotic fluid cells of the fetus and peripheral blood of his/her parents were extracted, respectively, and then performed WES. After the process of library construc-tion, hybrid capture and sequencing, the obtained data were compared with the database from human genome and literatures and ana-lyzed by software. The pathogenic mutations were searched based on the American College of Medical Genetics and Genomics ( ACMG, 2015) guideline and verified by the Sanger sequencing. Results The WES results found that the compound heterozygous mutations ex-isted in POMT1 gene of the fetus, which were inherited from the splice site mutation c.605+1G>A( IVS7) of his/her mother and the frameshift mutation c.1367 c.1368 ( exon 15) insGA, p. L456Lfs?80 of his/her father, respectively. The Sanger sequencing results were consistent with that of WES. The fetus was affected by Walker-Warburg syndrome, and his/her parents decided to terminate the pregnancy finally. Conclusion The WES may diagnose Walker-Warburg syndrome rapidly and accurately, which may play an impor-tant role in clinical management and genetic counseling.

Prenatal diagnosis of two fetuses with chromosome 1p36 deletion syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze two fetuses with multiple malformations revealed by ultrasonography using single nucleotide polymorphism array (SNP array), and to explore the strategy for the prenatal diagnosis of 1p36 deletion syndrome.</p><p><b>METHODS</b>Amniocentesis was performed on the two pregnant women. Amnion fluid cells were cultured, and karyotypes of the fetuses were determined through G-banding analysis. Whole genome SNP array was used to detect genomic anomalies of the two fetuses. The karyotypes of their parents were determined through G-banding analysis of peripheral venous blood samples.</p><p><b>RESULTS</b>G-banding analysis showed a 46,XY,add(1p36)? and a 46,XX,add(1p36)? karyotype for fetuses 1 and 2, respectively. SNP array analysis showed that the fetus 1 had arr[19]1p36.33p36.32 (752 566 - 3 393 462)×1 and 7q35q36.3 (144 480 549 - 159 119 486)×3, and fetus 2 had arr[19]1p36.33p36.23 (752 566 - 8 362 754)×1, 6p25.3p22.3 (204 909 - 20 182 185)×3. The mother of fetus 1 had a 46,XX,t(1;7)(p36;q35) karyotype, and the mother of fetus 2 had a 46,XX,t(1;6)(p36;p22) karyotype. The karyotypes of both fathers appeared to be normal.</p><p><b>CONCLUSION</b>SNP array has the advantages such as high sensitivity and high accuracy for prenatal diagnosis, and can provide more detailed information for genetic counseling of 1p36 deletion syndrome.</p>

Detection of TSC1/TSC2 gene mutations among patients with tuberous sclerosis complex by Ion Torrent semiconductor sequencing / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To develop and validate a method for mutation screening and prenatal diagnosis of TSC1/TSC2 mutations among patients with tuberous sclerosis complex (TSC) by Ion Torrent semiconductor sequencing.</p><p><b>METHODS</b>Potential mutations of SC1/TSC2 gene was detected in 2 TSC families and 1 sporadic TSC patient using an Ion Torrent PGM sequencer. Candidate variants were validated by Sanger sequencing. The corresponding site of TSC2 in the fetus of family 2 was also detected with Sanger sequencing.</p><p><b>RESULTS</b>Ion Torrent semiconductor sequencing has identified a probably pathogenic TSC2 mutation (c.311-312insGCTG) in the patient from family 1, and a probably pathogenic TSC2 mutation (c.1790A>G) in the patient of family 2.</p><p><b>CONCLUSION</b>Targeted Ion Torrent PGM sequencing is an accurate and efficient method to detect TSC1/TSC2 mutations in TSC.</p>

Array comparative genomic hybridization detection of a de novo 4q21.21-q22.1 deletion in a child with severe growth retardation / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze a child with developmental delay, severe mental retardation, speech delay and muscular hypotonia.</p><p><b>METHODS</b>The karotypes of the child and her parents were analyzed with G-banding analysis. Their genome DNA was also analyzed with array comparative genomic hybridization (array-CGH).</p><p><b>RESULTS</b>No karyotypic abnormality was detected at cytogenetic level. However, array-CGH has identified a de novo 4q21.21-q22.1 deletion in the child, which has a size of 12.1 Mb.</p><p><b>CONCLUSION</b>The de novo interstitial 4q21.21-q22.1 deletion probably underlies the main clinical manifestation in the child. Array-CGH is useful for diagnosing children with multiple congenital anomalies with unclear etiology.</p>