Porterboje9633

OBJECTIVE To explore the genetic basis for a child with autism spectrum disorder (ASD) and congenital heart disease. METHODS G-banded chromosomal karyotyping was carried out for the patient and his parents. The child was also subjected to whole exome sequencing (WES) and low-coverage massively parallel copy number variation sequencing (CNV-seq). The result was validated by chromosomal microarray analysis (CMA). RESULTS The karyotype of the patient and his parents were normal. No significant genetic variation was found by WES. However, CNV-seq has discovered a 47, XY, +21 [10%]/46,XY [90%] mosaicism in the patient. The result was confirmed by CMA. CONCLUSION In addition to Down syndrome, low proportion mosaic trisomy 21 is also associated with ASD. WES and CNV-seq can enable accurate diagnosis for patient with unexplained ASD.OBJECTIVE To detect chromosomal aberrations in two fetuses with multiple malformation. METHODS The two fetuses were subjected to chromosomal microarray analysis (CMA) by using Affymetrix CytoScan 750K arrays. The results were analyzed by bioinformatic software. RESULTS CMA analysis suggested that both fetuses harbored pathogenic copy number variations (CNVs) in the 2p15-16.1 region, which ranged from 255 kb to 257 kb and encompassed the XPO1 and USP34 genes. CONCLUSION Deletion of the chr2 (61 659 957-61 733 075, hg19) encompassing the XPO1 and USP34 genes may underlie the multiple malformations in the two fetuses.OBJECTIVE To perform prenatal diagosis for two fetuses carrying partial deletion of Y chromosome. METHODS Routine G- and C-banding were carried out to analyze the chromosomal karyotypes of the fetuses and their fathers. Fetal DNA was also subjected to low-coverage massively parallel copy number variation sequencing (CNV-seq), fluorescence in situ hybridization (FISH), SRY gene and AZF factor testing. RESULTS Both fetuses showed a 46, XN, del(Y) (q11.2) karyotype at 320-400 band level by the analysis of amniotic fluid chromosomes. FISH with Y chromosome centromere probe indicated that in both cases the number of Y chromosome was normal. Both fathers had an apparently normal karyotype at 320-400 band level. For fetus 1, CNV-seq test revealed a 12.88 Mb deletion at Yq11.221-q12, which encompassed the whole of AZFb+AZFc regions and may lead to male infertility, sperm deficiency and/or severe oligospermia. In fetus 2, CNV-seq also detected a 14.84 Mb deletion at Yq11.21-q12, which encompassed the whole of the AZF region and may lead to severe spermatogenesis disorder resulting in severe oligoasthenospermia and azoospermia. In both cases, testing of SRY gene was positive. No point mutation of the SRY gene was identified. ABBV-744 mw Analysis of amniotic fluid DNA confirmed partial or total absence of AZF in the two fetuses, respectively. CONCLUSION Combined use of various technologies can enable accurate detection of structural abnormalities of the Y chromosome and facilitate genetic counseling. CNV-seq can help with rapid screening of Y chromosome microdeletions and may be used as a complementary test for chromosomal karyotyping.OBJECTIVE To explore the genetic etiology of a child with autism, mental retardation and epilepsy. METHODS Conventional G-banding chromosomal analysis was carried out. Chromosomal variation was also detected by single nucleotide polymorphism microarray (SNP array). Pathogenic mutations were screened by high-throughput sequencing and validated by Sanger sequencing. Pathologic significance of the candidate mutations was analyzed through search of database and literature review. RESULTS No karyotypic abnormality was found with the child and his parents, while SNP array has detected a 460 kb deletion in the 14q11.2 region in the child. High-throughput and Sanger sequencing revealed a novel mutation of the NALCN gene in the child, in addition with a hemizygous mutation of the COL4A5 gene in the child and his mother. CONCLUSION The 14q11.2 microdeletion and NALCN mutation may contribute to the autism, mental retardation and epilepsy in this child.OBJECTIVE To explore the genetic basis for a child featuring delayed language development. METHODS The patient was subjected to conventional G-banding chromosomal karyotyping and single nucleotide polymorphism microarray (SNP array) analysis. RESULTS The karyotype of the child was 46, XY, r(22)(p11.2q13). SNP array analysis has identified a hemizygous 1.67 Mb deletion at 22q13 (arr [Hg19]22q13.33 (49 531 302-51 197 766)×1). CONCLUSION The child has carried a ring 22 in addition with a 22q13 microdeletion. The results may provide clues for her condition and genetic counseling for the family.OBJECTIVE To explore the basis for a child with multiple malformations and correlate her genotype with phenotype. METHODS The child was subjected to G-banding chromosomal analysis first, and low-coverage massively parallel copy number variation sequencing (CNV-seq) was used to define the aberrant region. The results were verified by fluorescence in situ hybridization (FISH). RESULTS The child was found to have a karyotype of 46,XX,3pter+?. CNV-seq has identified a 13.5 Mb duplication at 10p13p15.3(60 466-13 556 655) and a 636 kb microdeletion at 3p26.3 (60 064-695 821). Her karyotype was the refore specified as 46, XX, ish der(3) t(3;10) (10p+,3pdim) by FISH. Both of her parents were normal, which suggested an de novo origin of the above variant. CONCLUSION The de novo 10p13p15.3 duplication probably underlies the mental retardation, development delay, dysmorphism, and gastroesophageal reflux in the child. The CHL1 gene from the 3p26.3 region may play an important role in the formation and function of the brain, which may underlie the intellectual deficit in this child.OBJECTIVE To detect variant of APOE gene in a Chinese Tibetan patient with lipoprotein glomerulopathy (LPG) confirmed by renal biopsy and to explore its pathogenesis. METHODS Clinical and pathological data was collected. DNA was extracted from peripheral blood sample of the patient and subjected to PCR and Sanger sequencing. Pathogenicity of the variant was analyzed by bioinformatics software. RESULTS Renal biopsy of the patient has confirmed the diagnosis of LPG. DNA sequencing suggested that the patient has carried a heterozygous c.527G>C (p.R176P) variant of the APOE gene (APOE Osaka/Kurashiki). Four cases of LPG have been found to carry the same variant, and the encoded amino acid (p.176R) is highly conserved during evolution. Bioinformatic analysis using SIFT, PolyPhen2 and PANTHER software all predicted the variant to be pathogenic. CONCLUSION The discovery of author's patient provided further evidence for the pathogenicity of APOE Osaka/Kurashiki and, more importantly, provide new evidence for the multiracial origin of LPG-related APOE variants.