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Genetic Diagnostic Elucidation of a Patient With Multiorgan Granulomas, Facial Peculiarities, and Psychomotor Retardation
We report the case of a 19-years-old patient who presented with a perplexing variety of symptoms which included remarkable facial features, intellectual disability, granulomatous upper lip swelling (previously diagnosed as Melkersson–Rosenthal syndrome), Crohn’s-like disease, non-productive cough, a...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170790/ https://www.ncbi.nlm.nih.gov/pubmed/30319683 http://dx.doi.org/10.3389/fgene.2018.00355 |
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author | Soukup, Daniel Kuechler, Alma Roesler, Joachim Pichlmaier, Leopold Eckerland, Maximillian Olivier, Margarete Stehling, Florian |
author_facet | Soukup, Daniel Kuechler, Alma Roesler, Joachim Pichlmaier, Leopold Eckerland, Maximillian Olivier, Margarete Stehling, Florian |
author_sort | Soukup, Daniel |
collection | PubMed |
description | We report the case of a 19-years-old patient who presented with a perplexing variety of symptoms which included remarkable facial features, intellectual disability, granulomatous upper lip swelling (previously diagnosed as Melkersson–Rosenthal syndrome), Crohn’s-like disease, non-productive cough, and a granulomatous mass localized in the left lung. Chronic granulomatous disease (CGD) was diagnosed using dihydrorhodamine 123 assay that showed low levels of phagocytic NADPH-oxidase. DNA sequencing revealed a heterozygous mutation in the NCF-1 gene on chromosome 7. As remarkable facial features and psychomotor retardation are not associated with CGD, a more detailed genetic work-up using fluorescence in situ hybridization was performed. A microdeletion in 7q11.23 on one allele indicated Williams–Beuren syndrome (WBS). The NCF-1 gene and its two pseudogenes are part of a highly repetitive region within 7q11.23 and are prone to recombination events and deletions. Such deletions can involve both the WBS critical region and the NCF-1 wildtype gene, as was the case for our patient. The second allele of the NCF-1 gene was affected by the frequent c.75.76delGT mutation that stems from a recombination of the NCF-1 wildtype gene with one of its pseudogenes. In conclusion, patients with NCF-1-deficient CGD may also harbor microdeletions that result in WBS or other hereditary disorders; therefore, it is important to perform a thorough genetic analysis in order to initiate appropriate therapy for these patients. |
format | Online Article Text |
id | pubmed-6170790 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-61707902018-10-12 Genetic Diagnostic Elucidation of a Patient With Multiorgan Granulomas, Facial Peculiarities, and Psychomotor Retardation Soukup, Daniel Kuechler, Alma Roesler, Joachim Pichlmaier, Leopold Eckerland, Maximillian Olivier, Margarete Stehling, Florian Front Genet Genetics We report the case of a 19-years-old patient who presented with a perplexing variety of symptoms which included remarkable facial features, intellectual disability, granulomatous upper lip swelling (previously diagnosed as Melkersson–Rosenthal syndrome), Crohn’s-like disease, non-productive cough, and a granulomatous mass localized in the left lung. Chronic granulomatous disease (CGD) was diagnosed using dihydrorhodamine 123 assay that showed low levels of phagocytic NADPH-oxidase. DNA sequencing revealed a heterozygous mutation in the NCF-1 gene on chromosome 7. As remarkable facial features and psychomotor retardation are not associated with CGD, a more detailed genetic work-up using fluorescence in situ hybridization was performed. A microdeletion in 7q11.23 on one allele indicated Williams–Beuren syndrome (WBS). The NCF-1 gene and its two pseudogenes are part of a highly repetitive region within 7q11.23 and are prone to recombination events and deletions. Such deletions can involve both the WBS critical region and the NCF-1 wildtype gene, as was the case for our patient. The second allele of the NCF-1 gene was affected by the frequent c.75.76delGT mutation that stems from a recombination of the NCF-1 wildtype gene with one of its pseudogenes. In conclusion, patients with NCF-1-deficient CGD may also harbor microdeletions that result in WBS or other hereditary disorders; therefore, it is important to perform a thorough genetic analysis in order to initiate appropriate therapy for these patients. Frontiers Media S.A. 2018-09-27 /pmc/articles/PMC6170790/ /pubmed/30319683 http://dx.doi.org/10.3389/fgene.2018.00355 Text en Copyright © 2018 Soukup, Kuechler, Roesler, Pichlmaier, Eckerland, Olivier and Stehling. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Soukup, Daniel Kuechler, Alma Roesler, Joachim Pichlmaier, Leopold Eckerland, Maximillian Olivier, Margarete Stehling, Florian Genetic Diagnostic Elucidation of a Patient With Multiorgan Granulomas, Facial Peculiarities, and Psychomotor Retardation |
title | Genetic Diagnostic Elucidation of a Patient With Multiorgan Granulomas, Facial Peculiarities, and Psychomotor Retardation |
title_full | Genetic Diagnostic Elucidation of a Patient With Multiorgan Granulomas, Facial Peculiarities, and Psychomotor Retardation |
title_fullStr | Genetic Diagnostic Elucidation of a Patient With Multiorgan Granulomas, Facial Peculiarities, and Psychomotor Retardation |
title_full_unstemmed | Genetic Diagnostic Elucidation of a Patient With Multiorgan Granulomas, Facial Peculiarities, and Psychomotor Retardation |
title_short | Genetic Diagnostic Elucidation of a Patient With Multiorgan Granulomas, Facial Peculiarities, and Psychomotor Retardation |
title_sort | genetic diagnostic elucidation of a patient with multiorgan granulomas, facial peculiarities, and psychomotor retardation |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170790/ https://www.ncbi.nlm.nih.gov/pubmed/30319683 http://dx.doi.org/10.3389/fgene.2018.00355 |
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