A NOVEL MISSENSE MUTATION OUTSIDE DNAJ DOMAIN OF DNAJC21 IS ASSOCIATED WITH SHWACHMAN-DIAMOND SYNDROME

Shwachman-Diamond Syndrome (SDS) and related bone marrow failure disorders are characterized by early onset pancytopenia with a hypocellular bone marrow, short stature, and pancreatic insufficiency, along with an increased risk for myeloid malignancies. Recently, several cases with an SDS-like syndr...

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Autores principales:	Mohammad Bilal Alsavaf, Fatma Zehra Okus, Alper Ozcan, Ekrem Unal, Jeffrey M. Verboon, Vijay G. Sankaran, Muhammed E. Dogan, Munis Dundar, Zehra Busra Azizoglu, Ahmet Eken, Hamiyet Donmez Altıuntas
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Diseases of the blood and blood-forming organs RC633-647.5
Acceso en línea:	https://doaj.org/article/d6e37a0e897841d895391efe3b1b3f8a
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spelling	oai:doaj.org-article:d6e37a0e897841d895391efe3b1b3f8a2021-11-10T04:38:50ZA NOVEL MISSENSE MUTATION OUTSIDE DNAJ DOMAIN OF DNAJC21 IS ASSOCIATED WITH SHWACHMAN-DIAMOND SYNDROME2531-137910.1016/j.htct.2021.10.1086https://doaj.org/article/d6e37a0e897841d895391efe3b1b3f8a2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2531137921012335https://doaj.org/toc/2531-1379Shwachman-Diamond Syndrome (SDS) and related bone marrow failure disorders are characterized by early onset pancytopenia with a hypocellular bone marrow, short stature, and pancreatic insufficiency, along with an increased risk for myeloid malignancies. Recently, several cases with an SDS-like syndrome have been reported to harbor mutations in the DNAJ domain of DNAJC21. Here, we report an intriguing case of a 13.5 years-old female born to Turkish consanguineous parents with a novel missense mutation occurring outside the DNAJ domain of the DNAJC21 gene. Whole-exome and Sanger sequencing confirmation revealed a homozygous missense mutation in DNAJC21 gene c.463T>C, p.W155R which was considered as pathogenic in in silico analyses. Initially, this patient's vague and atypical symptoms led to uncertainty of the underlying diagnosis. Upon confirmation of the genetic mutation, a number of functional studies such as diepoxibutane test, proliferation test from peripheral blood mononuclear cells, and cytokinesis-block micronucleus cytome assay performed with the patient cells confirmed the likely diagnosis of an SDS-like syndrome attributable to DNAJC21 dysfunction. Through the analysis of this rare case, we illuminate the pleiotropic features of this unique bone marrow failure syndrome and emphasize the paramount role of genomic testing to discriminate a range of closely related bone marrow failure disorders.Mohammad Bilal AlsavafFatma Zehra OkusAlper OzcanEkrem UnalJeffrey M. VerboonVijay G. SankaranMuhammed E. DoganMunis DundarZehra Busra AzizogluAhmet EkenHamiyet Donmez AltıuntasElsevierarticleDiseases of the blood and blood-forming organsRC633-647.5ENHematology, Transfusion and Cell Therapy, Vol 43, Iss , Pp S61-S62 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diseases of the blood and blood-forming organs RC633-647.5
spellingShingle	Diseases of the blood and blood-forming organs RC633-647.5 Mohammad Bilal Alsavaf Fatma Zehra Okus Alper Ozcan Ekrem Unal Jeffrey M. Verboon Vijay G. Sankaran Muhammed E. Dogan Munis Dundar Zehra Busra Azizoglu Ahmet Eken Hamiyet Donmez Altıuntas A NOVEL MISSENSE MUTATION OUTSIDE DNAJ DOMAIN OF DNAJC21 IS ASSOCIATED WITH SHWACHMAN-DIAMOND SYNDROME
description	Shwachman-Diamond Syndrome (SDS) and related bone marrow failure disorders are characterized by early onset pancytopenia with a hypocellular bone marrow, short stature, and pancreatic insufficiency, along with an increased risk for myeloid malignancies. Recently, several cases with an SDS-like syndrome have been reported to harbor mutations in the DNAJ domain of DNAJC21. Here, we report an intriguing case of a 13.5 years-old female born to Turkish consanguineous parents with a novel missense mutation occurring outside the DNAJ domain of the DNAJC21 gene. Whole-exome and Sanger sequencing confirmation revealed a homozygous missense mutation in DNAJC21 gene c.463T>C, p.W155R which was considered as pathogenic in in silico analyses. Initially, this patient's vague and atypical symptoms led to uncertainty of the underlying diagnosis. Upon confirmation of the genetic mutation, a number of functional studies such as diepoxibutane test, proliferation test from peripheral blood mononuclear cells, and cytokinesis-block micronucleus cytome assay performed with the patient cells confirmed the likely diagnosis of an SDS-like syndrome attributable to DNAJC21 dysfunction. Through the analysis of this rare case, we illuminate the pleiotropic features of this unique bone marrow failure syndrome and emphasize the paramount role of genomic testing to discriminate a range of closely related bone marrow failure disorders.
format	article
author	Mohammad Bilal Alsavaf Fatma Zehra Okus Alper Ozcan Ekrem Unal Jeffrey M. Verboon Vijay G. Sankaran Muhammed E. Dogan Munis Dundar Zehra Busra Azizoglu Ahmet Eken Hamiyet Donmez Altıuntas
author_facet	Mohammad Bilal Alsavaf Fatma Zehra Okus Alper Ozcan Ekrem Unal Jeffrey M. Verboon Vijay G. Sankaran Muhammed E. Dogan Munis Dundar Zehra Busra Azizoglu Ahmet Eken Hamiyet Donmez Altıuntas
author_sort	Mohammad Bilal Alsavaf
title	A NOVEL MISSENSE MUTATION OUTSIDE DNAJ DOMAIN OF DNAJC21 IS ASSOCIATED WITH SHWACHMAN-DIAMOND SYNDROME
title_short	A NOVEL MISSENSE MUTATION OUTSIDE DNAJ DOMAIN OF DNAJC21 IS ASSOCIATED WITH SHWACHMAN-DIAMOND SYNDROME
title_full	A NOVEL MISSENSE MUTATION OUTSIDE DNAJ DOMAIN OF DNAJC21 IS ASSOCIATED WITH SHWACHMAN-DIAMOND SYNDROME
title_fullStr	A NOVEL MISSENSE MUTATION OUTSIDE DNAJ DOMAIN OF DNAJC21 IS ASSOCIATED WITH SHWACHMAN-DIAMOND SYNDROME
title_full_unstemmed	A NOVEL MISSENSE MUTATION OUTSIDE DNAJ DOMAIN OF DNAJC21 IS ASSOCIATED WITH SHWACHMAN-DIAMOND SYNDROME
title_sort	novel missense mutation outside dnaj domain of dnajc21 is associated with shwachman-diamond syndrome
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/d6e37a0e897841d895391efe3b1b3f8a
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A NOVEL MISSENSE MUTATION OUTSIDE DNAJ DOMAIN OF DNAJC21 IS ASSOCIATED WITH SHWACHMAN-DIAMOND SYNDROME

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