Infancy onset diabetes mellitus in a patient with a novel homozygous LRBA mutation

<h3>Background</h3><p dir="ltr"><a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lipopolysaccharide" target="_blank">LRBA</a> deficiency is associated with <a href="https://www.sciencedirect....

وصف كامل

محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Iman Hawari (12561958) (author)
مؤلفون آخرون: Basma Haris (12040355) (author), Idris Mohammed (751020) (author), Johan Ericsson (49714) (author), Amel Khalifa (13020780) (author), Khalid Hussain (110443) (author)
منشور في: 2022
الموضوعات:
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author Iman Hawari (12561958)
author2 Basma Haris (12040355)
Idris Mohammed (751020)
Johan Ericsson (49714)
Amel Khalifa (13020780)
Khalid Hussain (110443)
author2_role author
author
author
author
author
author_facet Iman Hawari (12561958)
Basma Haris (12040355)
Idris Mohammed (751020)
Johan Ericsson (49714)
Amel Khalifa (13020780)
Khalid Hussain (110443)
author_role author
dc.creator.none.fl_str_mv Iman Hawari (12561958)
Basma Haris (12040355)
Idris Mohammed (751020)
Johan Ericsson (49714)
Amel Khalifa (13020780)
Khalid Hussain (110443)
dc.date.none.fl_str_mv 2022-02-21T09:00:00Z
dc.identifier.none.fl_str_mv 10.1016/j.jecr.2022.100108
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Infancy_onset_diabetes_mellitus_in_a_patient_with_a_novel_homozygous_LRBA_mutation/29022266
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biological sciences
Genetics
Biomedical and clinical sciences
Medical biochemistry and metabolomics
Oncology and carcinogenesis
Paediatrics
LRBA
Diabetes mellitus
Whole genome sequencing
Immunodeficiency
dc.title.none.fl_str_mv Infancy onset diabetes mellitus in a patient with a novel homozygous LRBA mutation
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <h3>Background</h3><p dir="ltr"><a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lipopolysaccharide" target="_blank">LRBA</a> deficiency is associated with <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/common-variable-immunodeficiency" target="_blank">common variable immune deficiency</a> which manifests as <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/hypogammaglobulinemia" target="_blank">hypogammaglobulinemia</a>, autoimmunity, <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/humoral-immune-deficiency" target="_blank">antibodies deficiency</a>, <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/lymphocyte-proliferation" target="_blank">lymphoproliferation</a> and a high susceptibility to <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/inflammatory-bowel-disease" target="_blank">inflammatory bowel disease</a> in early childhood. Diabetes mellitus, <a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/growth-retardation" target="_blank">growth retardation</a> and short stature have also been reported in some patients with <a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/lipopolysaccharide" target="_blank">LRBA</a> deficiency</p><h3>Methodology</h3><p dir="ltr">The <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/proband" target="_blank">proband</a> with infancy-onset diabetes mellitus was recruited with her family. <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/glutamate-decarboxylase" target="_blank">Glutamic acid decarboxylase</a>, insulin, <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/protein-tyrosine-phosphatase" target="_blank">protein tyrosine phosphatase</a> and <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/zinc-transporter" target="_blank">zinc transporter</a> autoantibodies were measured. <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/whole-genome-sequencing" target="_blank">Whole genome sequencing</a> for the proband was undertaken to identify causative gene and candidate mutations were confirmed using <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/sanger-sequencing" target="_blank">Sanger sequencing</a>. A diagram of <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/lipopolysaccharide" target="_blank">LRBA</a> with predicted domains and reported mutations of LRBA in patients diagnosed with diabetes mellitus was used to investigate clinical phenotype relation to genotype in this type of patients.</p><h3>Results</h3><p dir="ltr">Here we report a novel homozygous mutation <i>in LRBA</i> (W1330*, c.3999 G > A) in a child diagnosed with immunodeficiency and infancy-onset diabetes mellitus at the age of 7 months. The same mutation was also found in an older sibling but that sibling does not have diabetes mellitus. The heterogeneity of diabetes presentation in LRBA-deficient patients suggests other <a href="https://www.sciencedirect.com/topics/immunology-and-microbiology/heredity" target="_blank">genetic factors</a> or protein-protein interactions in the LRBA pathway may play a role in the pathogenesis of the disease</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Clinical and Translational Endocrinology: Case Reports<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.jecr.2022.100108" target="_blank">https://dx.doi.org/10.1016/j.jecr.2022.100108</a></p>
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spelling Infancy onset diabetes mellitus in a patient with a novel homozygous LRBA mutationIman Hawari (12561958)Basma Haris (12040355)Idris Mohammed (751020)Johan Ericsson (49714)Amel Khalifa (13020780)Khalid Hussain (110443)Biological sciencesGeneticsBiomedical and clinical sciencesMedical biochemistry and metabolomicsOncology and carcinogenesisPaediatricsLRBADiabetes mellitusWhole genome sequencingImmunodeficiency<h3>Background</h3><p dir="ltr"><a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lipopolysaccharide" target="_blank">LRBA</a> deficiency is associated with <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/common-variable-immunodeficiency" target="_blank">common variable immune deficiency</a> which manifests as <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/hypogammaglobulinemia" target="_blank">hypogammaglobulinemia</a>, autoimmunity, <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/humoral-immune-deficiency" target="_blank">antibodies deficiency</a>, <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/lymphocyte-proliferation" target="_blank">lymphoproliferation</a> and a high susceptibility to <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/inflammatory-bowel-disease" target="_blank">inflammatory bowel disease</a> in early childhood. Diabetes mellitus, <a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/growth-retardation" target="_blank">growth retardation</a> and short stature have also been reported in some patients with <a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/lipopolysaccharide" target="_blank">LRBA</a> deficiency</p><h3>Methodology</h3><p dir="ltr">The <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/proband" target="_blank">proband</a> with infancy-onset diabetes mellitus was recruited with her family. <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/glutamate-decarboxylase" target="_blank">Glutamic acid decarboxylase</a>, insulin, <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/protein-tyrosine-phosphatase" target="_blank">protein tyrosine phosphatase</a> and <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/zinc-transporter" target="_blank">zinc transporter</a> autoantibodies were measured. <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/whole-genome-sequencing" target="_blank">Whole genome sequencing</a> for the proband was undertaken to identify causative gene and candidate mutations were confirmed using <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/sanger-sequencing" target="_blank">Sanger sequencing</a>. A diagram of <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/lipopolysaccharide" target="_blank">LRBA</a> with predicted domains and reported mutations of LRBA in patients diagnosed with diabetes mellitus was used to investigate clinical phenotype relation to genotype in this type of patients.</p><h3>Results</h3><p dir="ltr">Here we report a novel homozygous mutation <i>in LRBA</i> (W1330*, c.3999 G > A) in a child diagnosed with immunodeficiency and infancy-onset diabetes mellitus at the age of 7 months. The same mutation was also found in an older sibling but that sibling does not have diabetes mellitus. The heterogeneity of diabetes presentation in LRBA-deficient patients suggests other <a href="https://www.sciencedirect.com/topics/immunology-and-microbiology/heredity" target="_blank">genetic factors</a> or protein-protein interactions in the LRBA pathway may play a role in the pathogenesis of the disease</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Clinical and Translational Endocrinology: Case Reports<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.jecr.2022.100108" target="_blank">https://dx.doi.org/10.1016/j.jecr.2022.100108</a></p>2022-02-21T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.jecr.2022.100108https://figshare.com/articles/journal_contribution/Infancy_onset_diabetes_mellitus_in_a_patient_with_a_novel_homozygous_LRBA_mutation/29022266CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/290222662022-02-21T09:00:00Z
spellingShingle Infancy onset diabetes mellitus in a patient with a novel homozygous LRBA mutation
Iman Hawari (12561958)
Biological sciences
Genetics
Biomedical and clinical sciences
Medical biochemistry and metabolomics
Oncology and carcinogenesis
Paediatrics
LRBA
Diabetes mellitus
Whole genome sequencing
Immunodeficiency
status_str publishedVersion
title Infancy onset diabetes mellitus in a patient with a novel homozygous LRBA mutation
title_full Infancy onset diabetes mellitus in a patient with a novel homozygous LRBA mutation
title_fullStr Infancy onset diabetes mellitus in a patient with a novel homozygous LRBA mutation
title_full_unstemmed Infancy onset diabetes mellitus in a patient with a novel homozygous LRBA mutation
title_short Infancy onset diabetes mellitus in a patient with a novel homozygous LRBA mutation
title_sort Infancy onset diabetes mellitus in a patient with a novel homozygous LRBA mutation
topic Biological sciences
Genetics
Biomedical and clinical sciences
Medical biochemistry and metabolomics
Oncology and carcinogenesis
Paediatrics
LRBA
Diabetes mellitus
Whole genome sequencing
Immunodeficiency