Olsenmckee2081

To carried out prenatal diagnosis and genetic analysis for a case with Nail-patella syndrome.

Based on the clinical phenotype and prenatal imaging, genetic testing and prenatal diagnosis were carried out through whole exome sequencing (WES) and Sanger sequencing.

Analysis of amniotic fluid showed that the fetus has carried a heterozygous c.139+1G>T splicing site variant [Chr9(GRCh37) g.129376868G>T] of the LMX1B gene, which was verified by Sanger sequencing. The same heterozygous variant was found in the pregnant woman, her daughter and her mother but not in her husband. Searching of HGMD database showed that the c.139+1G>T was previously unreported.

Nail-patella syndrome is an autosomal dominant genetic disorder with various clinical manifestations. WES is helpful for its genetic and prenatal diagnosis.

Nail-patella syndrome is an autosomal dominant genetic disorder with various clinical manifestations. WES is helpful for its genetic and prenatal diagnosis.

To explore the genetic basis of a patient presenting with dysmorphism, intellectual disability, psychomotor delay and hypoplasia of corpus callosum by using next generation sequencing.

Genomic DNA was extracted from peripheral blood samples of the patient and his family members and subjected to exome sequencing. Suspected variants were verified with Sanger sequencing.

The patient was found to carry a heterozygous c.1357delAinsGGA variant in exon 11 of the TCF4 gene, which was verified as de novo by Sanger sequencing. The variant may result in a truncated protein and affect its function.

The heterozygous c.1357delAinsGGA variant the TCF4 gene probably underlies the disease in the proband.

The heterozygous c.1357delAinsGGA variant the TCF4 gene probably underlies the disease in the proband.

To analyze the phenotype and genotype of a patient affected with inherited antithrombin deficiency.

All exons and exon-intron boundaries of the AT genes were subjected to PCR amplification and Sanger sequencing. The influence of variants on the disease was predicted using bioinformatic software (MutationTaster).

The results of all coagulation tests were normal, though the antithrombin activity and antigen content of the proband and his father have decreased significantly (34%, 48% and 12.97 mg/dL, 15.60 mg/dL, respectively). His mother was normal. Genetic analysis revealed that the proband and his father both carried a heterozygous g.2736dupT variant of the AT gene. Bioinformatic analysis suggested that the variant may be pathogenic.

The proband and his father both had type I hereditary antithrombin deficiency caused by a g.2736dupT variant of the AT gene. The variant was unreported previously.

The proband and his father both had type I hereditary antithrombin deficiency caused by a g.2736dupT variant of the AT gene. The variant was unreported previously.

To explore the genetic basis for a child with neonatal severe hyperparathyroidism.

Genomic DNA was extracted from peripheral blood samples from the patient and her parents. Whole exome sequencing was carried out to screen potential mutations. Suspected mutation was verified by Sanger sequencing.

The proband was found to carry compound heterozygous variants c.179G>A (p.Cys60Tyr) and c.1525G>A (p.Gly509Arg) of the CaSR gene. The c.179G>A variant was derived from her mother and was unreported previously. The c.1525G>A variant was derived from her father and known to be pathogenic.

The compound heterozygous variants of c.179G>A and c.1525G>A of the CaSR gene probably underlie the disease in the patient. The results of genetic testing has enabled diagnosis and genetic counseling for her family.

A of the CaSR gene probably underlie the disease in the patient. The results of genetic testing has enabled diagnosis and genetic counseling for her family.

To explore the genetic basis for a pedigree affected with Charcot-Marie-Tooth (CMT) disease through high-throughput sequencing.

Potential variants of the genes associated with CMT were screened by next-generation sequencing (NGS) of the members of the pedigree.

NGS has revealed that the two affected sisters both harbored homozygous c.1A>G variant of the GDAP1 gene, which caused replacement of the first amino acid Methionine by Valine (p.Met1Val). Their parents were both carriers of the heterozygous c.1A>G variant. The variant was unreported previously and has an extremely low frequency in the population. Meanwhile, one of the sisters and the mother also carried heterozygous c.710A>T variant of the BAG3 gene.

The homozygous c.1A>G variant of the GDAP1 gene probably underlay the CMT in both children. Above result has enabled clinical diagnosis and genetic counseling for this pedigree.

G variant of the GDAP1 gene probably underlay the CMT in both children. Above result has enabled clinical diagnosis and genetic counseling for this pedigree.

To analyze the molecular etiology of a Chinese child affected with dihydropyrimidinase deficiency.

Genomic DNA was extracted from peripheral blood samples of the family members. Pathogenic variant was determined by whole exome sequencing and verified by Sanger sequencing.

The child was found to harbor homozygous c.905G>A (p.Arg302Gln) variants in exon 5 of the DPYS gene, for which her parents were both heterozygous carriers.

The homozygous c.905G>A (p.Arg302Gln) variants of the DPYS gene probably underlies the dihydropyrimidinase deficiency in the child. Above result has enabled genetic counseling and prenatal diagnosis for this family.

A (p.Arg302Gln) variants of the DPYS gene probably underlies the dihydropyrimidinase deficiency in the child. Above result has enabled genetic counseling and prenatal diagnosis for this family.

To explore the effect of rare synonymous variants of the ATP7B gene on the splicing of its precursor mRNA.

A total of 248 rare synonymous variants with allelic frequency of <0.005 were retrieved from the ExAc database. Human Splicing Finder (HSF) was used to predict their effect on the splicing of precursor mRNA. And ESE Finder 3.0 was used to predict the effect of such variants on the binding ability of SR protein family. Rare synonymous variants affecting the binding of two or more SR proteins were selected and verified with an in vitro mini gene splicing report system.

HSF analysis indicated that 136 of the 248 rare synonymous variants may destroy the exonic splicing enhancer (ESE) motif. Analysis using ESE Finder 3.0 indicated that 19 of them may affect the binding of two or more SR proteins at the same time. APX-115 concentration In vitro mini gene experiment confirmed that the c.1620C>T (p.L540L) and c.3888C>T (p.A1296A) variants could lead to abnormal splicing of the corresponding exons, resulting in complete skipping of exon 4 and 25% increase in the skipping of exon 18, respectively.