OBJECTIVE: To analyze variants of TSC1 and TSC2 genes in a Chinese patient with tuberous sclerosis complex (TSC). METHODS: Peripheral blood samples were collected from the patient and her parents with informed consent. Following extraction of genomic DNA, potential variants of the TSC1 and TSC2 genes was detected by using targeted capture next-generation sequencing (NGS) and Sanger sequencing. RESULTS: The patient was found to harbor a de novo mosaicism variant c.3295_3298delG (Val1100CysfsTer3) of the TSC2 gene, with the proportion of the mutant allele determined as 13.4%, which was confirmed by Sanger sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.3295_3298delG (Val1100CysfsTer3) variant was predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION The mosaicism heterozygous variant of c.3295_3298delG of the TSC2 gene, as detected by both NGS and Sanger sequencing, probably underlay the TSC2 in this patient.
Female ; Humans ; Mosaicism ; Mutation ; Tuberous Sclerosis/genetics* ; Tuberous Sclerosis Complex 1 Protein/genetics* ; Tuberous Sclerosis Complex 2 Protein/genetics*

OBJECTIVE: To analyze the clinical phenotype of a Chinese pedigree affected with Tuberous sclerosis complex (TSC) and explore pathogenic mutations of TSC1 and TSC2 gene. METHODS: Unique clinical phenotypes，the results of imaging, examination of the proband and special family history, collectively, made the constellation of features of TSC. Genomic DNA was obtained from six affected and eight unaffected members of the family and potential mutations of the TSC1 and TSC2 genes were detected by PCR-amplification of the exons and exon-intron boundaries and direct sequencing. A total of 150 normal unrelated individuals were used as controls. RESULTS: Genetic analysis documented the presence of a heterozygous mutation, c.1781_1782delTG (p.Val594GlyfsX11), in the exon 15 of TSC1 gene within all the patients of the family. This mutation was not observed in the eight unaffected family members or in the 150 unrelated control subjects from the same population , or the Human Gene Mutation Database (HGMD) and had completely co-segregated with the disease phenotype in the family. CONCLUSION The c.1781_1782delTG mutation of TSC1 gene may be responsible for the tuberous sclerosis complex in this family. The data presented in the present study are of significance to clinicians, as well as genetic counselors, and may provide new clues for molecular diagnosis of this disease．.
DNA Mutational Analysis ; Humans ; Mutation ; Pedigree ; Tuberous Sclerosis ; genetics ; Tuberous Sclerosis Complex 1 Protein ; genetics ; Tuberous Sclerosis Complex 2 Protein

OBJECTIVE: To analyze the clinical features of a Chinese pedigree affected with tuberculosis sclerosis and explore its molecular pathogenesis. METHODS: Clinical data of the proband and members of his pedigree were collected. Whole exome sequencing was carried out to detect variants of the TSC1 and TSC2 genes. Candidate variants was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The proband and his mother, who also had mild features of tuberous sclerosis, were found to harbor a novel heterozygous c.4183C>T (p.Q1395X) variant of the TSC2 gene, which was absent in the 4 healthy relatives. Bioinformatic analysis suggested the variant to be likely pathogenic. CONCLUSION The heterozygous c.4183C>T (p.Q1395X) variant of the TSC2 gene probably underlay the disease in this pedigree. Above finding has expanded the spectrum of TSC2 gene variants. The more severe symptoms in the proband may be attributed to phenotypic heterogeneity of this disease.
China ; Humans ; Mutation ; Pedigree ; Tuberous Sclerosis/genetics* ; Tuberous Sclerosis Complex 2 Protein/genetics*

OBJECTIVE: To explore the genetic basis for a patient diagnosed with tuberous sclerosis complex (TSC). METHODS: Peripheral blood samples of the patient and his parents were collected for the extraction of genomic DNA. Next generation sequencing (NGS) was carried out to detect potential variant, and the result was verified by Sanger sequencing. RESULTS: The patient was found to harbor a heterozygous c.1053delG (p.Glu352SerfsX10) frameshifting variant of the TSC2 gene. The same variant was not found in his unaffected parents and 100 unrelated healthy controls. Based on the American College of Medical Genetics and Genomics guidelines, the variant was predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION The novel c.1053delG (p.Glu352SerfsX10) frameshifting variant of the TSC2 gene probably underlay the TSC in this patient.
Genomics ; Heterozygote ; Humans ; Mutation ; Tuberous Sclerosis/genetics* ; Tuberous Sclerosis Complex 2 Protein/genetics*

OBJECTIVE: To identify pathogenic mutation of TSC1 and TSC2 genes in a patient with long-time misdiagnosis of epilepsy. METHODS: Peripheral blood samples and clinical data of the patient and her 2 parents were collected. Potential mutation of TSC1 and TSC2 genes were detected by direct sequencing. RESULTS: The patient had frequent episodes of epilepsy in addition with Shagreen patches for 10 years. A frame-shifting mutation c.2509_2512delAACA was detected in exon 20 of the TSC1 gene. This same mutation was not found in her unaffected parents. CONCLUSION The recurrent frame-shifting mutation c.2509_2512delAACA (p.Asn837ValfsX11) of the TSC1 gene probably underlies the disease in this patient.
Diagnostic Errors ; Epilepsy ; diagnosis ; genetics ; Female ; Frameshift Mutation ; Humans ; Tuberous Sclerosis ; diagnosis ; genetics ; Tuberous Sclerosis Complex 1 Protein ; genetics ; Tuberous Sclerosis Complex 2 Protein ; genetics

OBJECTIVE: To explore the genetic basis for a patient with tuberous sclerosis complex. METHODS: Genomic DNA was extracted from peripheral blood samples from members of his family and 100 unrelated healthy controls. The proband was subjected to next-generation sequencing, and candidate variant was confirmed by multiple ligation-dependent probe amplification (MLPA) and Sanger sequencing. Reverse transcription-PCR (RT-PCR) was carried out to determine the relative mRNA expression in the proband. RESULTS: The patient was found to harbor a c.2355+1G>C splicing variant of the TSC2 gene. Sequencing of cDNA confirmed that 62 bases have been inserted into the 3' end of exon 21, which has caused a frameshift producing a truncated protein. CONCLUSION The novel splicing variant c.2355+1G>C of the TSC2 gene probably underlay the TSC in the proband. Above finding has expanded the variant spectrum of TSC2 and provided a basis for preimplantation genetic testing and/or prenatal diagnosis.
Female ; Humans ; Mutation ; Pregnancy ; RNA Splicing/genetics* ; Tuberous Sclerosis/genetics* ; Tuberous Sclerosis Complex 1 Protein/genetics* ; Tuberous Sclerosis Complex 2 Protein/genetics*

OBJECTIVE: To carry out genetic testing and prenatal diagnosis for 29 Chinese pedigrees affected with tuberous sclerosis complex (TSC) and assess efficacy of combined next generation sequencing (NGS) and multiple ligation-dependent probe amplification (MLPA) for the diagnosis. METHODS: NGS and MLPA were used in conjunct to detect variants of TSC1 and TSC2 genes among the probands of the pedigrees. Paternity test was carried out to exclude maternal DNA contamination. Prenatal diagnosis was provided to 14 couples based on the discoveries in the probands. RESULTS: Twenty-seven variants were identified in the TSC1 and TSC2 genes among the 29 pedigrees, which yielded a detection rate of 93.1%. Respectively, 5 (18.5%) and 22 (81.5%) variants were identified in the TSC1 and TSC2 genes. Twelve variants were unreported previously. Prenatal diagnosis showed that five fetuses were affected with TSC, whilst the remaining nine were unaffected. CONCLUSION Above finding has expanded the spectrum of TSC1 and TSC2 gene variants. Combined NGS and MLPA has enabled diagnosis of TSC with efficiency and accuracy.
DNA Mutational Analysis ; Female ; Genetic Testing ; Humans ; Mutation ; Pregnancy ; Prenatal Diagnosis ; Tuberous Sclerosis/genetics* ; Tuberous Sclerosis Complex 1 Protein/genetics* ; Tuberous Sclerosis Complex 2 Protein/genetics*

Epilepsy ; etiology ; Female ; Humans ; Infant ; Tuberous Sclerosis ; complications ; diagnosis ; genetics

OBJECTIVE: To explore the clinical characteristics and genetic variant in a neonate with tuberous sclerosis complex (TSC). METHODS: Clinical data of the neonate was collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to next-generation sequencing (NGS). RESULTS: The child was noted to have yellowish hair upon birth. NGS revealed that he has harbored a heterozygous c.3914del (p.P1305Rfs*20) frameshifting variant of the TSC2 gene. The variant has probably caused premature termination of translation, resulting in a truncated protein. CONCLUSION Yellowish hair has rarely been described as the first manifestation of TSC. The c.3914del (p.P1305Rfs*20) variant of the TSC2 gene probably underlay the TSC in this patient.
Male ; Infant, Newborn ; Humans ; Tuberous Sclerosis/genetics* ; Family ; Carotenoids ; Heterozygote

OBJECTIVE: To explore the genetic basis for Chinese pedigree affected with tuberous sclerosis complex (TSC). METHODS: The proband and his family members were subjected to Sanger sequencing for variants of the TSC1 and TSC2 genes. RESULTS: The proband was found to harbor a c.2837+1dupG splicing variant at a donor site of the TSC2 gene. The same variant was not found among his family members and the fetus during his mother's subsequent pregnancy. CONCLUSION The c.2837+1dupG splicing variant of the TSC2 gene has probably predisposed to the TSC in this pedigree. Above finding has enriched the spectrum of pathogenic variants associated with this disease.
Female ; Genetic Testing ; Humans ; Male ; Mutation ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Tuberous Sclerosis/genetics* ; Tuberous Sclerosis Complex 2 Protein/genetics*