Objective To investigate clinical features and detect mutations in a case of tuberous sclerosis complex (TSC) caused by a somatic mosaic mutation in the TSC2 gene.Methods Peripheral blood samples were obtained from a patient with suspected TSC,his parents,and 200 unrelated healthy controls.Genomic DNA was extracted from these blood samples,polymerase chain reaction (PCR)and nextgeneration sequencing were performed to amplify all the exons and their flanking sequences of the TSC 1 and TSC2 genes followed by DNA sequencing,so as to identify mutations in the TSC 1 and TSC2 genes.DNA was also extracted from lesional skin tissues of the patient,and PCR was conducted to amplify the target fragment of the TSC2 gene followed by DNA sequencing.Results The patient clinically presented with facial angiofibroma,depigmented patches on the waist,periungual fibroma and angioleio-myolipoma of the kidney,which were consistent with the diagnosis of TSC.A mutation c.5130_5131insT(p.V1711Cfs* 18) was identified in the TSC2 gene in the patient.A higher frequency of the mutation was found in the DNA of the tumor tissue than in that of the peripheral blood.No such a mutation was found in his parents'DNA,unrelated healthy controls or any public database.Conclusion The somatic mosaic mutation c.5130_513 1insT in the TSC2 gene is responsible for the phenotype of TSC in the patient.

OBJECTIVE: To carry out genetic testing and prenatal diagnosis for a woman featuring moderate intellectual disability (ID). METHODS: The patient had presented at the First Affiliated Hospital of Zhengzhou University on April 28, 2021. With informed consent, peripheral blood and amniotic fluid samples were collected for the extraction of genomic DNA. Pathogenic copy number variations (CNVs) were detected with CNV-seq, and single gene variants were detected by whole exome sequencing (WES) and Sanger sequencing. Candidate variant was verified by Sanger sequencing, and CNV-seq and multiplex ligation-dependent probe amplification (MLPA) were used to detect fetal CNVs. RESULTS: The 23-year-old woman had moderate ID, sideway walking, and unstable holding. Ultrasonography at 18⁺³ weeks' gestation had revealed no fetal abnormality. No pathogenic CNV was detected in the woman by CNV-Seq, while WES revealed that she has harbored a heterozygous c.1675C>T (p.Arg559*) variant of the DLG4 gene, which was verified by Sanger sequencing. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic (PVS1+PM2_supporting). Sanger sequencing has confirmed that the fetus has inherited this variant, and CNV-Seq also revealed that that fetus has harbored a 0.1 Mb heterozygous deletion at Xp21.1, which has encompassed the DMD gene, and the result was verified by MLPA. CONCLUSION The heterozygous c.1675C>T variant of the DLG4 gene probably underlay the mental retardation in this woman, and her fetus was found to harbor the same variant in addition with deletion of the DMD gene, which may predispose to ID type 62.
Female ; Humans ; Pregnancy ; Young Adult ; Disks Large Homolog 4 Protein ; DNA Copy Number Variations ; Fetus ; Genetic Testing ; Intellectual Disability/genetics* ; Pregnant Women