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Two different genetic etiologies for tuberous sclerosis complex (TSC) in a single family

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic condition that involves abnormalities of the skin, hamartomas in the heart, brain, and kidneys, seizures, as well as TSC‐associated neuropsychiatric disorders (TAND). About 90%–95% of individuals with TSC will have an iden...

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Autores principales: Mowrey, Kate, Koenig, Mary Kay, Szabo, Charles A., Samuels, Joshua, Mulligan, Shannon, Pearson, Deborah A., Northrup, Hope
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336739/
https://www.ncbi.nlm.nih.gov/pubmed/32383331
http://dx.doi.org/10.1002/mgg3.1296
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author Mowrey, Kate
Koenig, Mary Kay
Szabo, Charles A.
Samuels, Joshua
Mulligan, Shannon
Pearson, Deborah A.
Northrup, Hope
author_facet Mowrey, Kate
Koenig, Mary Kay
Szabo, Charles A.
Samuels, Joshua
Mulligan, Shannon
Pearson, Deborah A.
Northrup, Hope
author_sort Mowrey, Kate
collection PubMed
description BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic condition that involves abnormalities of the skin, hamartomas in the heart, brain, and kidneys, seizures, as well as TSC‐associated neuropsychiatric disorders (TAND). About 90%–95% of individuals with TSC will have an identifiable pathogenic variant in either TSC1 or TSC2. We present here two family members with clinical diagnoses of TSC that were later determined to be due to two different genetic etiologies. METHODS: A 2‐year‐old Caucasian female (Patient 1) was born to non‐consanguineous healthy parents and was determined to have a clinical diagnosis of TSC at 2 months old. Her paternal great‐uncle (Patient 2) was also known to have a clinical diagnosis of TSC. Sequencing and deletion/duplication analysis for TSC1 and TSC2 were performed on both individuals. RESULTS: Mutation analysis revealed that both Patient 1 and Patient 2 had identifiable pathogenic variants in TSC2. Patient 1 had c.4800_4801delTG (p.Cys1600Trpfs*2), while Patient 2 had c.4470_4471delinsTT (p.Glu1490_Lys1491delinsAsp*). CONCLUSION: To our knowledge, our clinical report is of significance as it is the third kindred to be identified with affected members with two distinct genetic etiologies for TSC. Our case report highlights the importance of incorporating genetic testing into the clinical evaluation for individuals with features suggestive of TSC.
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spelling pubmed-73367392020-07-08 Two different genetic etiologies for tuberous sclerosis complex (TSC) in a single family Mowrey, Kate Koenig, Mary Kay Szabo, Charles A. Samuels, Joshua Mulligan, Shannon Pearson, Deborah A. Northrup, Hope Mol Genet Genomic Med Clinical Reports BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic condition that involves abnormalities of the skin, hamartomas in the heart, brain, and kidneys, seizures, as well as TSC‐associated neuropsychiatric disorders (TAND). About 90%–95% of individuals with TSC will have an identifiable pathogenic variant in either TSC1 or TSC2. We present here two family members with clinical diagnoses of TSC that were later determined to be due to two different genetic etiologies. METHODS: A 2‐year‐old Caucasian female (Patient 1) was born to non‐consanguineous healthy parents and was determined to have a clinical diagnosis of TSC at 2 months old. Her paternal great‐uncle (Patient 2) was also known to have a clinical diagnosis of TSC. Sequencing and deletion/duplication analysis for TSC1 and TSC2 were performed on both individuals. RESULTS: Mutation analysis revealed that both Patient 1 and Patient 2 had identifiable pathogenic variants in TSC2. Patient 1 had c.4800_4801delTG (p.Cys1600Trpfs*2), while Patient 2 had c.4470_4471delinsTT (p.Glu1490_Lys1491delinsAsp*). CONCLUSION: To our knowledge, our clinical report is of significance as it is the third kindred to be identified with affected members with two distinct genetic etiologies for TSC. Our case report highlights the importance of incorporating genetic testing into the clinical evaluation for individuals with features suggestive of TSC. John Wiley and Sons Inc. 2020-05-08 /pmc/articles/PMC7336739/ /pubmed/32383331 http://dx.doi.org/10.1002/mgg3.1296 Text en © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Clinical Reports
Mowrey, Kate
Koenig, Mary Kay
Szabo, Charles A.
Samuels, Joshua
Mulligan, Shannon
Pearson, Deborah A.
Northrup, Hope
Two different genetic etiologies for tuberous sclerosis complex (TSC) in a single family
title Two different genetic etiologies for tuberous sclerosis complex (TSC) in a single family
title_full Two different genetic etiologies for tuberous sclerosis complex (TSC) in a single family
title_fullStr Two different genetic etiologies for tuberous sclerosis complex (TSC) in a single family
title_full_unstemmed Two different genetic etiologies for tuberous sclerosis complex (TSC) in a single family
title_short Two different genetic etiologies for tuberous sclerosis complex (TSC) in a single family
title_sort two different genetic etiologies for tuberous sclerosis complex (tsc) in a single family
topic Clinical Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336739/
https://www.ncbi.nlm.nih.gov/pubmed/32383331
http://dx.doi.org/10.1002/mgg3.1296
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