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Cortical atrophy and hypofibrinogenemia due to FGG and TBCD mutations in a single family: a case report

BACKGROUND: Blended phenotypes or co-occurrence of independent phenotypically distinct conditions are extremely rare and are due to coincidence of multiple pathogenic mutations, especially due to consanguinity. Hereditary fibrinogen deficiencies result from mutations in the genes FGA, FGB, and FGG,...

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Autores principales: Stephen, Joshi, Nampoothiri, Sheela, Vinayan, K. P., Yesodharan, Dhanya, Remesh, Preetha, Gahl, William A., Malicdan, May Christine V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956920/
https://www.ncbi.nlm.nih.gov/pubmed/29769041
http://dx.doi.org/10.1186/s12881-018-0597-6
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author Stephen, Joshi
Nampoothiri, Sheela
Vinayan, K. P.
Yesodharan, Dhanya
Remesh, Preetha
Gahl, William A.
Malicdan, May Christine V.
author_facet Stephen, Joshi
Nampoothiri, Sheela
Vinayan, K. P.
Yesodharan, Dhanya
Remesh, Preetha
Gahl, William A.
Malicdan, May Christine V.
author_sort Stephen, Joshi
collection PubMed
description BACKGROUND: Blended phenotypes or co-occurrence of independent phenotypically distinct conditions are extremely rare and are due to coincidence of multiple pathogenic mutations, especially due to consanguinity. Hereditary fibrinogen deficiencies result from mutations in the genes FGA, FGB, and FGG, encoding the three different polypeptide chains that comprise fibrinogen. Neurodevelopmental abnormalities have not been associated with fibrinogen deficiencies. In this study, we report an unusual patient with a combination of two independently inherited genetic conditions; fibrinogen deficiency and early onset cortical atrophy. CASE PRESENTATION: The study describes a male child from consanguineous family presented with hypofibrinogenemia, diffuse cortical atrophy, microcephaly, hypertonia and axonal motor neuropathy. Through a combination of homozygosity mapping and exome sequencing, we identified bi-allelic pathogenic mutations in two genes: a homozygous novel truncating mutation in FGG (c.554del; p.Lys185Argfs*14) and a homozygous missense mutation in TBCD (c.1423G > A;p.Ala475Thr). Loss of function mutations in FGG have been associated with fibrinogen deficiency, while the c.1423G > A mutation in TBCD causes a novel syndrome of neurodegeneration and early onset encephalopathy. CONCLUSIONS: Our study highlights the importance of homozygosity mapping and exome sequencing in molecular prenatal diagnosis, especially when multiple gene mutations are responsible for the phenotype. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12881-018-0597-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-59569202018-05-24 Cortical atrophy and hypofibrinogenemia due to FGG and TBCD mutations in a single family: a case report Stephen, Joshi Nampoothiri, Sheela Vinayan, K. P. Yesodharan, Dhanya Remesh, Preetha Gahl, William A. Malicdan, May Christine V. BMC Med Genet Case Report BACKGROUND: Blended phenotypes or co-occurrence of independent phenotypically distinct conditions are extremely rare and are due to coincidence of multiple pathogenic mutations, especially due to consanguinity. Hereditary fibrinogen deficiencies result from mutations in the genes FGA, FGB, and FGG, encoding the three different polypeptide chains that comprise fibrinogen. Neurodevelopmental abnormalities have not been associated with fibrinogen deficiencies. In this study, we report an unusual patient with a combination of two independently inherited genetic conditions; fibrinogen deficiency and early onset cortical atrophy. CASE PRESENTATION: The study describes a male child from consanguineous family presented with hypofibrinogenemia, diffuse cortical atrophy, microcephaly, hypertonia and axonal motor neuropathy. Through a combination of homozygosity mapping and exome sequencing, we identified bi-allelic pathogenic mutations in two genes: a homozygous novel truncating mutation in FGG (c.554del; p.Lys185Argfs*14) and a homozygous missense mutation in TBCD (c.1423G > A;p.Ala475Thr). Loss of function mutations in FGG have been associated with fibrinogen deficiency, while the c.1423G > A mutation in TBCD causes a novel syndrome of neurodegeneration and early onset encephalopathy. CONCLUSIONS: Our study highlights the importance of homozygosity mapping and exome sequencing in molecular prenatal diagnosis, especially when multiple gene mutations are responsible for the phenotype. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12881-018-0597-6) contains supplementary material, which is available to authorized users. BioMed Central 2018-05-16 /pmc/articles/PMC5956920/ /pubmed/29769041 http://dx.doi.org/10.1186/s12881-018-0597-6 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Case Report
Stephen, Joshi
Nampoothiri, Sheela
Vinayan, K. P.
Yesodharan, Dhanya
Remesh, Preetha
Gahl, William A.
Malicdan, May Christine V.
Cortical atrophy and hypofibrinogenemia due to FGG and TBCD mutations in a single family: a case report
title Cortical atrophy and hypofibrinogenemia due to FGG and TBCD mutations in a single family: a case report
title_full Cortical atrophy and hypofibrinogenemia due to FGG and TBCD mutations in a single family: a case report
title_fullStr Cortical atrophy and hypofibrinogenemia due to FGG and TBCD mutations in a single family: a case report
title_full_unstemmed Cortical atrophy and hypofibrinogenemia due to FGG and TBCD mutations in a single family: a case report
title_short Cortical atrophy and hypofibrinogenemia due to FGG and TBCD mutations in a single family: a case report
title_sort cortical atrophy and hypofibrinogenemia due to fgg and tbcd mutations in a single family: a case report
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956920/
https://www.ncbi.nlm.nih.gov/pubmed/29769041
http://dx.doi.org/10.1186/s12881-018-0597-6
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