Novel TSC1 mutation associated with variable phenotypes in tuberous sclerosis

2013 ◽  
Vol 154 (23) ◽  
pp. 914-918 ◽  
Author(s):  
Erzsébet Kövesdi ◽  
Kinga Hadzsiev ◽  
Katalin Komlósi ◽  
Mária Kassay ◽  
Péter Barsi ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
De Novo ◽  
Phenotypic Variability ◽  
Molecular Genetic ◽  
Clinical Signs ◽  
Renal Cysts ◽  
Molecular Genetic Analysis ◽  
Autosomal Dominant Disorder ◽  
Modifying Factors ◽  
Tsc1 Gene

Tuberous sclerosis is an autosomal dominant disorder, caused by mutations of the TSC1 or TSC2 genes resulting in tumor predisposition. Clinical signs include non-malignant brain tumors, skin, eye, heart and kidney abnormalities. The authors report a Hungarian family with broad phenotypic variability. First, the 5-year-old boy, showing the most symptoms was examined, whose first seizure occurred at 15 months and a cranial magnetic resonance imaging revealed numerous intracerebral calcareous foci. Except of hypopigmented skin spots, no other abnormality was found on physical examination. The mother was completely asymptomatic. Epilepsy of the maternal uncle started at the age of 3 years, of his sister at the age of 17 years and of the maternal grandmother at the age of 39 years. At the age of 52 years the grandmother developed renal cysts. Molecular genetic analysis of the family confirmed a de novo heterozygous point mutation (c.2523 C\>T) in exon 20 of the TSC1 gene. The mutation was detected in all examined family members. Despite increasing data on the pathomechanism of tuberous sclerosis, there is still little known about the genetic modifying factors influencing the broad intra- and interfamilial phenotypic variability. Orv. Hetil., 2013, 154, 914–918.

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

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.

scholarly journals Prenatal Sonographic Features of CHARGE Syndrome

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 415
Author(s):  
Kuntharee Traisrisilp ◽  
Wisit Chankhunaphas ◽  
Rekwan Sittiwangkul ◽  
Chureerat Phokaew ◽  
Vorasuk Shotelersuk ◽  
...  
Keyword(s):  
De Novo ◽  
Heart Defects ◽  
Molecular Genetic ◽  
Choanal Atresia ◽  
Charge Syndrome ◽  
Acoustic Stimulation ◽  
Genetic Mutation ◽  
Suspected Case ◽  
Autosomal Dominant Disorder ◽  
Canal Stenosis

CHARGE syndrome is a rare autosomal dominant disorder, associated with coloboma (C), heart defects (H), choanal atresia (A), retardation of growth and/or central nervous system (R), genitourinary anomalies (G) and ear abnormalities (E). Prenatal diagnosis of the syndrome is very rare but may be suspected when a combination of such abnormalities is identified. We describe a prenatally suspected case of CHARGE syndrome due to unique findings of cardiac defects (DORV) in combination with minor clues, including a structurally malformed ear with persistent non-response to an acoustic stimulation (which has never been prenatally described elsewhere), renal malrotation and growth restriction. Postnatal diagnosis was made based on confirmation of the prenatal findings and additional specific findings of bilateral coloboma, choanal atresia and ear canal stenosis. Finally, molecular genetic testing by whole exome sequencing of the neonate and her parents revealed a novel de novo heterozygous frameshift c.3506_3509dup variant in the CHD7 gene, confirming the clinical diagnosis of CHARGE syndrome. In conclusion, we describe unique prenatal features of CHARGE syndrome. Educationally, this is one of the rare examples of CHARGE syndrome, comprising all of the six specific anomalies as originally described; it is also supported by the identification of a specific genetic mutation. The identified genetic variant has never been previously reported, thereby expanding the mutational spectrum of CHD7. Finally, this case can inspire prenatal sonographers to increase awareness of subtle or minor abnormalities as genetic sonomarkers.

Genetic Etiologies, Diagnosis, and Treatment of Tuberous Sclerosis Complex

2019 ◽  
Vol 20 (1) ◽  
pp. 217-240 ◽  
Author(s):  
Catherine L. Salussolia ◽  
Katarzyna Klonowska ◽  
David J. Kwiatkowski ◽  
Mustafa Sahin
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Phenotypic Variability ◽  
Mtor Inhibitors ◽  
Multiple Organ ◽  
Great Promise ◽  
Optimal Timing ◽  
Autosomal Dominant Disorder ◽  
Organ Systems ◽  
Neuropsychiatric Manifestations

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that affects multiple organ systems due to an inactivating variant in either TSC1 or TSC2, resulting in the hyperactivation of the mechanistic target of rapamycin (mTOR) pathway. Dysregulated mTOR signaling results in increased cell growth and proliferation. Clinically, TSC patients exhibit great phenotypic variability, but the neurologic and neuropsychiatric manifestations of the disease have the greatest morbidity and mortality. TSC-associated epilepsy occurs in nearly all patients and is often difficult to treat because it is refractory to multiple antiseizure medications. The advent of mTOR inhibitors offers great promise in the treatment of TSC-associated epilepsy and other neurodevelopmental manifestations of the disease; however, the optimal timing of therapeutic intervention is not yet fully understood.

Application and evaluation of denaturing HPLC for molecular genetic analysis in tuberous sclerosis

2000 ◽  
Vol 106 (6) ◽  
pp. 663-668 ◽  
Author(s):  
Alistair C. Jones ◽  
Julian R. Sampson ◽  
Bastian Hoogendoorn ◽  
David Cohen ◽  
Jeremy P. Cheadle
Keyword(s):  
Genetic Analysis ◽  
Tuberous Sclerosis ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis

Molecular genetic analysis of a de novo balanced translocation t(6;17)(p21.31;q11.2) associated with hypospadias and anorectal malformation

2006 ◽  
Vol 119 (1-2) ◽  
pp. 162-168 ◽  
Author(s):  
Mahmoud Reza Mansouri ◽  
Birgit Carlsson ◽  
Edward Davey ◽  
Agneta Nordenskjöld ◽  
Tomas Wester ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Anorectal Malformation ◽  
De Novo ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Balanced Translocation

Application and evaluation of denaturing HPLC for molecular genetic analysis in tuberous sclerosis

2000 ◽  
Vol 106 (6) ◽  
pp. 663-668 ◽  
Author(s):  
Alistair C. Jones ◽  
Julian R. Sampson ◽  
Bastian Hoogendoorn ◽  
David Cohen ◽  
Jeremy P. Cheadle
Keyword(s):  
Genetic Analysis ◽  
Tuberous Sclerosis ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis

Unusual clinical manifestations of type 1 neurofibromatosis

2011 ◽  
Vol 152 (49) ◽  
pp. 1965-1970
Author(s):  
Katalin Komlósi ◽  
Noémi Polgár ◽  
Kinga Hadzsiev ◽  
Gábor Ottóffy ◽  
Tamás Illés ◽  
...  
Keyword(s):  
Phenotypic Variability ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Final Diagnosis ◽  
Molecular Genetic Analysis ◽  
Café Au Lait Spots ◽  
Type 1 Neurofibromatosis ◽  
The Central Nervous System ◽  
Neurofibromin 1

Type 1 neurofibromatosis is an autosomal dominant hamartosis caused by mutations of the neurofibromin-1 gene. The classic features of the clinical phenotype include the presence of café-au-lait spots, neurofibromas, axillary and inguinal freckling, Lisch-nodules and deformities of the skeletal system, as well as the risk of developing multiple tumors, especially in the central nervous system. However, it is known from the literature that the phenotypic variability can pose a huge diagnostic difficulty. Aims: Our institute performs molecular genetic testing of the neurofibromin-1 gene since 2008; during this period several unusual phenotypic variants were found. Results, conclusion: The reported four cases represent interesting phenotypic variants or diagnostic challenges in which the final diagnosis was established by molecular genetic analysis. Orv. Hetil., 2011, 152, 1965–1970.

scholarly journals Genome Sequence of the Oleaginous Red Yeast Rhodosporidium toruloides MTCC 457

2012 ◽  
Vol 11 (8) ◽  
pp. 1083-1084 ◽  
Author(s):  
Shailesh Kumar ◽  
Hariom Kushwaha ◽  
Anand Kumar Bachhawat ◽  
Gajendra Pal Singh Raghava ◽  
Kaliannan Ganesan
Keyword(s):  
Genome Sequence ◽  
De Novo ◽  
Molecular Genetic ◽  
Draft Genome ◽  
Molecular Genetic Analysis ◽  
Rhodosporidium Toruloides ◽  
Biofuel Production ◽  
Content Type ◽  
Oleaginous Fungi ◽  
Red Yeast

ABSTRACTWe report thede novoassembled 20.05-Mb draft genome of the red yeastRhodosporidium toruloidesMTCC 457, predicted to encode 5,993 proteins, 4 rRNAs, and 125 tRNAs. Proteins known to be unique to oleaginous fungi are present among the predicted proteins. The genome sequence will be valuable for molecular genetic analysis and manipulation of lipid accumulation in this yeast and for developing it as a potential host for biofuel production.

Phenotypic Variability and mTOR Pathway Gene Aberrations in Familial Tuberous Sclerosis

2017 ◽  
Vol 15 (06) ◽  
pp. 316-324
Author(s):  
Shobana Sekar ◽  
Sara Nasser ◽  
Jonathan Adkins ◽  
Lori Cuyugan ◽  
Daniel Enriquez ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Autosomal Dominant ◽  
Phenotypic Variability ◽  
Severe Disease ◽  
Mtor Pathway ◽  
Autosomal Dominant Disorder ◽  
Blood Leukocytes ◽  
Dna And Rna ◽  
Pathway Gene ◽  
Gene Alterations

AbstractTuberous sclerosis complex (TSC) is an autosomal dominant disorder that demonstrates variable severity, such that affected family members may have mild or severe disease. We performed exome and RNA sequencing of blood leukocytes from mild and severe cases across four families to identify mTOR pathway aberrations that may underlie phenotypic variability. In each family, we identified TSC1/TSC2 aberrations along with different mTOR pathway gene alterations, including base substitutions, deletions, and skewed allelic frequencies. Here, we describe the first reported DNA and RNA analysis of TSC families demonstrating mTOR pathway aberrations in mild and severe forms of the disease.

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