Analysis of clinical phenotype and gene variants in a patient with classic tuberous sclerosis complex
10.35541/cjd.20210541
- VernacularTitle:典型结节性硬化症1例临床表型及基因变异分析
- Author:
Linli LIU
1
;
Gaowu YAN
;
Lingli DENG
;
Qinglian LU
;
Tingting LIU
;
Fei OUYANG
;
Chunshui YU
Author Information
1. 遂宁市中心医院皮肤科，遂宁 629000
- Keywords:
Tuberous sclerosis;
DNA mutational analysis;
TSC2 gene;
Minigene
- From:
Chinese Journal of Dermatology
2022;55(8):713-716
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze clinical phenotypes and pathogenic mutations of a patient with classic tuberous sclerosis complex.Methods:Clinical data was collected from a patient with classic tuberous sclerosis complex. Next-generation sequencing was performed to screen pathogenic gene variants, and Sanger sequencing to verify the mutations. Minigene plasmids were constructed and transfected into the human renal epithelial cell line 293T, and RNA was extracted for transcriptional analysis.Results:The patient clinically presented with recurrent epileptic seizures, facial angiofibroma, periungual fibroma, pulmonary lymphangioleiomyomatosis, renal angiomyolipoma and multiple osteosclerosis. Next-generation sequencing revealed a suspected pathogenic variant in the TSC2 gene in the patient. Sanger sequencing identified a heterozygous mutation c.336_336+15delGGTAAGGCCCAGGGCG in exon 4 of the TSC2 gene in the patient, but not in his parents or 100 unrelated healthy controls. Moreover, this mutation had not been previously reported. The minigene experiment showed changed mRNA sequence of the TSC2 gene in this patient with loss of the authentic splice site in exon 4 and insertion of a 74-bp intron, which shifted the splice site 90 bp downstream (r.336delins336+16_336+90) .Conclusion:The novel heterozygous mutation c.336_336+15delGGTAAGGCCCAGGGCG in exon 4 of the TSC2 gene can lead to aberrant splicing, and may contribute to tuberous sclerosis complex in this patient.
