A novel de novo mutation in the TSC2 gene in a Chinese patient with tuberous sclerosis complex

Tuberous Sclerosis Complex (TSC) is an autosomal dominant inherited neurocutaneous disorder. Tuberous Sclerosis Complex is caused by mutations in tumor suppressor gene (TSC), both TSC1 and TSC2. In approximately two-thirds of cases neither parent has signs of TSC and the disease is caused by a de novo mutation. Tuberous Sclerosis Complex is classically identified by the Vort's triad in the presence of angiofibroma, mental retardation, and epilepsy. A 17-year-old woman with a major complaint of a facial bump that appeared at birth and got bigger when she reached puberty. There are white patches on the patient's body from birth. On the scalp obtained the presence of skin color plaque, while at the back and right knee obtained shagreen patch. Patientwas diagnosed with epilepsy and mental retardation by the pediatric department. No family history has the same complaints as patient. Histopathologic examination of facial bumps taken by shaving biopsy suggests the presence of hemangiomas. Based on the clinical diagnostic criteria from International Tuberous Sclerosis Complex Consensus Conference 2012, the patient meets two major criteria, macular hypopigmentation and shagreen patch so it is included in "definite diagnosis".

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Renal Manifestations of Tuberous Sclerosis Complex

Journal of Kidney Cancer and VHL ◽

10.15586/jkcvhl.v7i3.131 ◽

2020 ◽

Vol 7 (3) ◽

pp. 5-19

Author(s):

Nikhil Nair ◽

Ronith Chakraborty ◽

Zubin Mahajan ◽

Aditya Sharma ◽

Sidarth Sethi ◽

...

Keyword(s):

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Gene Disruption ◽

Treatment Guidelines ◽

Renal Cysts ◽

Skin Lesions ◽

Multiple Organ ◽

Tsc2 Gene ◽

Genetic Condition ◽

Organ Systems

Tuberous sclerosis complex (TSC) is a genetic condition caused by a mutation in either the TSC1 or TSC2 gene. Disruption of either of these genes leads to impaired production of hamartin or tuberin proteins, leading to the manifestation of skin lesions, tumors and seizures. TSC can manifests in multiple organ systems with the cutaneous and renal systems being the most commonly affected. These manifestations can secondarily lead to the development of hypertension, chronic kidney disease, and neurocognitive declines. The renal pathologies most commonly seen in TSC are angiomyolipoma, renal cysts and less commonly, oncocytomas. In this review, we highlight the current understanding on the renal manifestations of TSC along with current diagnosis and treatment guidelines.

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A novel TSC1 variant associated with tuberous sclerosis and sacrococcygeal teratoma

Human Genome Variation ◽

10.1038/s41439-020-00124-8 ◽

2020 ◽

Vol 7 (1) ◽

Author(s):

Saba Ahmad ◽

Luis Manon ◽

Gifty Bhat ◽

Jerry Machado ◽

Alice Zalan ◽

...

Keyword(s):

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Cellular Differentiation ◽

Autosomal Dominant ◽

De Novo ◽

Autosomal Dominant Disease ◽

Sacrococcygeal Teratoma ◽

Dominant Disease ◽

The Brain

AbstractTuberous sclerosis complex (TSC) is an autosomal dominant disease associated with tumors and malformed tissues in the brain and other vital organs. We report a novel de novo frameshift variant of the TSC1 gene (c.434dup;p. Ser146Valfs*8) in a child with TSC who initially presented with a sacral teratoma. This previously unreported association between TSC and teratoma has broad implications for the pathophysiology of embryonic tumors and mechanisms underlying cellular differentiation.

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Combination of Multiple Ligation-Dependent Probe Amplification and Illumina MiSeq Amplicon Sequencing for TSC1/TSC2 Gene Analyses in Patients with Tuberous Sclerosis Complex

Journal of Molecular Diagnostics ◽

10.1016/j.jmoldx.2016.10.009 ◽

2017 ◽

Vol 19 (2) ◽

pp. 265-276 ◽

Cited By ~ 5

Author(s):

Nur Farrah Dila Ismail ◽

Abdul Qawee Rani ◽

Nik Mohd Ariff Nik Abdul Malik ◽

Chia Boon Hock ◽

Siti Nabilahuda Mohd Azlan ◽

...

Keyword(s):

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Illumina Miseq ◽

Amplicon Sequencing ◽

Tsc2 Gene ◽

Dependent Probe

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Early diagnosis of a newborn with tuberous sclerosis caused by a genetic mutation

Journal of International Medical Research ◽

10.1177/03000605211035895 ◽

2021 ◽

Vol 49 (8) ◽

pp. 030006052110358

Author(s):

Lin Qiao ◽

Yuting Yang ◽

Dongmei Yue

Keyword(s):

Genetic Testing ◽

Early Diagnosis ◽

Tuberous Sclerosis ◽

De Novo ◽

Clinical Manifestations ◽

De Novo Mutation ◽

Heterozygous Mutation ◽

Loss Of Function ◽

Autosomal Dominant Disorder ◽

Tsc1 Gene

Objective Tuberous sclerosis (TSC) is an autosomal dominant disorder, often detected during childhood. We present the results of genetic testing in a newborn with suspected TSC. Methods A newborn with no specific clinical manifestations of TSC showed evidence of TSC on magnetic resonance imaging and echocardiography. Next-generation sequencing (NGS) and multiple ligation-dependent probe amplification (MLPA) of the TSC1 and TSC2 gene exons were carried out to confirm the diagnosis. Results The results of MLPA were negative, but NGS showed a heterozygous mutation in the TSC1 gene comprising insertion of a T residue at c.2165 (exon 17) to c.2166 (exon 17), indicating a loss of function mutation. These results were verified by Sanger sequencing. This genetic change was present in the newborn but the parental genotypes were wild-type, indicating a de novo mutation. Conclusions In this case, a case of TSC caused by a heterozygous mutation in the TSC1 gene was confirmed by NGS sequencing. This indicates the suitability of genetic testing for the early diagnosis of clinically rare and difficult-to-diagnose diseases, to guide clinical treatment.

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