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A Chinese tuberous sclerosis complex family and a novel tuberous sclerosis complex-2 mutation.

Luo R, Cai Q, Mu D - Chin. Med. J. (2015)

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, West China Second University Hospital; Key Laboratory of Obstetric and Gynecologic and Pediatric Dieases and Birth Defects of Ministry of Education, Sichuan University, Chengdu, Sichuan 610041, China.

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The incidence of TSC in Chinese population is still unknown although case reports of Chinese TSC patients were documented... Two causative genes for TSC, TSC1 gene on chromosome 9q34 and TSC2 gene on chromosome16p13, have been identified in 1997 and 1993 respectively... Chinese TSC patients are more likely to have TSC2 missense and frame shift mutations... The proband, a 16-year-old male, first presented with frequent focal motor seizures at age of 6 years and was clinically diagnosed as TSC at age of 9 years... Physical examination found forehead fibrous plaque, facial angiofibromas [Figure 1a], hypopigmented macules, and shagreen patches on his back. [Figure 1b]... He has shown moderate mental retardation and failed to pass any academic examinations... Tuberous sclerosis complex 1 and TSC2 genes, the pathogenic genes of TSC, are indicated as tumor suppressor genes due to their function in regulation of cell growth and differentiation by inhibiting the mammalian target of rapamycin (mTOR) in the Akt-mTOR-S6kinase cell growth pathway... Mutations including nonsense mutations, small deletions, splice site changes, missense mutations, and sometimes large deletions or rearrangements can occur over the entire regions of TSC1 and TSC2... However, no hotspots have been found... In this report, the family had a frame-shift mutation (c. 3576_3577insA) in exon 29 of TSC2 gene detected by Sanger sequencing, the gold standard to detect gene mutations... The fact that this mutation was observed only in the patients of the family but not in other healthy family members and the 100 unrelated normal controls suggests that this mutation is pathogenic... This mutation cannot be found in the leiden open variation database, suggesting the sequence aberration is novel... The phenomenon of mosaicism can explain the difference in severity between the father and his children, but cannot explain that between the two children... Therefore, whether TSC caused by the same mutation would aggravate itself when transmitted to the next generation and result in severity differences between siblings needs to be further explored.

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(a) DNA sequencing of exon 29 of the tuberous sclerosis complex (TSC2) gene finds a c. 3576_3577insA mutation in three patients. (b) Sequence of exon 29 of the TSC2 gene in normal subjects.
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Figure 2: (a) DNA sequencing of exon 29 of the tuberous sclerosis complex (TSC2) gene finds a c. 3576_3577insA mutation in three patients. (b) Sequence of exon 29 of the TSC2 gene in normal subjects.

Mentions: This study was approved without restrictions by Medical Ethics Committee of Sichuan University, and informed consents were obtained from the patients or their parents. Blood (3 ml) was drawn for Sanger sequencing from the patients, their healthy family members, and 100 unrelated normal controls. By sequencing the polymerase chain reaction fragments of the entire coding region and the exon-intron boundaries of TSC1 and TSC2, we detected a novel frame-shift mutation (c. 3576_3577insA) in the TSC2 gene exon 29 in each of the three patients [Figure 2a]. The mutation was not observed in other healthy family members and the unrelated normal controls [Figure 2b].


A Chinese tuberous sclerosis complex family and a novel tuberous sclerosis complex-2 mutation.

Luo R, Cai Q, Mu D - Chin. Med. J. (2015)

(a) DNA sequencing of exon 29 of the tuberous sclerosis complex (TSC2) gene finds a c. 3576_3577insA mutation in three patients. (b) Sequence of exon 29 of the TSC2 gene in normal subjects.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837808&req=5

Figure 2: (a) DNA sequencing of exon 29 of the tuberous sclerosis complex (TSC2) gene finds a c. 3576_3577insA mutation in three patients. (b) Sequence of exon 29 of the TSC2 gene in normal subjects.
Mentions: This study was approved without restrictions by Medical Ethics Committee of Sichuan University, and informed consents were obtained from the patients or their parents. Blood (3 ml) was drawn for Sanger sequencing from the patients, their healthy family members, and 100 unrelated normal controls. By sequencing the polymerase chain reaction fragments of the entire coding region and the exon-intron boundaries of TSC1 and TSC2, we detected a novel frame-shift mutation (c. 3576_3577insA) in the TSC2 gene exon 29 in each of the three patients [Figure 2a]. The mutation was not observed in other healthy family members and the unrelated normal controls [Figure 2b].

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, West China Second University Hospital; Key Laboratory of Obstetric and Gynecologic and Pediatric Dieases and Birth Defects of Ministry of Education, Sichuan University, Chengdu, Sichuan 610041, China.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

The incidence of TSC in Chinese population is still unknown although case reports of Chinese TSC patients were documented... Two causative genes for TSC, TSC1 gene on chromosome 9q34 and TSC2 gene on chromosome16p13, have been identified in 1997 and 1993 respectively... Chinese TSC patients are more likely to have TSC2 missense and frame shift mutations... The proband, a 16-year-old male, first presented with frequent focal motor seizures at age of 6 years and was clinically diagnosed as TSC at age of 9 years... Physical examination found forehead fibrous plaque, facial angiofibromas [Figure 1a], hypopigmented macules, and shagreen patches on his back. [Figure 1b]... He has shown moderate mental retardation and failed to pass any academic examinations... Tuberous sclerosis complex 1 and TSC2 genes, the pathogenic genes of TSC, are indicated as tumor suppressor genes due to their function in regulation of cell growth and differentiation by inhibiting the mammalian target of rapamycin (mTOR) in the Akt-mTOR-S6kinase cell growth pathway... Mutations including nonsense mutations, small deletions, splice site changes, missense mutations, and sometimes large deletions or rearrangements can occur over the entire regions of TSC1 and TSC2... However, no hotspots have been found... In this report, the family had a frame-shift mutation (c. 3576_3577insA) in exon 29 of TSC2 gene detected by Sanger sequencing, the gold standard to detect gene mutations... The fact that this mutation was observed only in the patients of the family but not in other healthy family members and the 100 unrelated normal controls suggests that this mutation is pathogenic... This mutation cannot be found in the leiden open variation database, suggesting the sequence aberration is novel... The phenomenon of mosaicism can explain the difference in severity between the father and his children, but cannot explain that between the two children... Therefore, whether TSC caused by the same mutation would aggravate itself when transmitted to the next generation and result in severity differences between siblings needs to be further explored.

Show MeSH
Related in: MedlinePlus