A novel splice site mutation in WAS gene in patient with Wiskott-Aldrich syndrome and chronic colitis: a case report

Esmaeilzadeh, Hossein; Bordbar, Mohammadreza; Dastsooz, Hassan; Silawi, Mohammad; Fard, Mohammad Ali Farazi; Adib, Ali; Kafashan, Ali; Tabatabaei, Zahra; Sadeghipour, Forough; Faghihi, Mohammad Ali

doi:10.1186/s12881-018-0647-0

Cited by 6 publications

(5 citation statements)

References 18 publications

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“…It could be due to the loss of functional mutations in the WAS gene located in the X chromosome (position Xp11.22-p11.23), and the pathogenic mutations that occur within the exons and introns [ 54 , 55 ]. As previously reported, at least 49 mutations (either nonsense, missense, frameshift, splice site or complex) occurred in the WAS gene [ 15 , 50 , 51 , 52 , 56 , 57 , 58 , 59 ].…”

Section: Immune Thrombocytopenia and Autoimmune Diseasesmentioning

confidence: 89%

A Review on Secondary Immune Thrombocytopenia in Malaysia

et al. 2021

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Immune thrombocytopenia (ITP) is an acquired autoimmune disease that occurs in adults and children. In Malaysia, the clinical practice guideline (CPG) for the management of ITP was issued in 2006, which focused almost exclusively on primary ITP (pITP), and only a few secondary ITP (sITP) forms were addressed. All published (twenty-three) sITP articles among children and adults in Malaysia, identified on the academic databases were retrieved. The articles were published between 1981 and 2019, at a rate of 0.62 publications per year. The publications were considered low and mainly focused on rare presentation and followed-up of secondary diseases. This review revealed that sITP in Malaysia is commonly associated with autoimmune diseases (Evan’s syndrome, SLE and WAS), malignancy (Kaposi’s sarcoma and breast cancer) and infection (dengue haemorrhagic fever, Helicobacter pylori and hepatitis C virus). The relationship between ITP and autoimmune diseases, malignancy and infections raise the question concerning the mechanism involved in these associations. Further studies should be conducted to bridge the current knowledge gap, and the further information is required to update the existing CPG of management of ITP in Malaysia.

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Section: Immune Thrombocytopenia and Autoimmune Diseasesmentioning

confidence: 89%

A Review on Secondary Immune Thrombocytopenia in Malaysia

et al. 2021

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“…In conclusion, Wiskott-Aldrich syndrome is a rare X-linked disorder that predominantly affects males. Male patients with congenital thrombocytopenia and small platelets must have their WAS gene mutation and WASP expression evaluated as soon as possible using molecular genetic techniques and protein detection [ 22 ]. In this study, we identified a novel pathogenic WAS gene mutation (c.931 + 5G > C (splicing)) causing XLT with mild clinical manifestations.…”

Section: Discussionmentioning

confidence: 99%

A Novel Splicing Mutation Leading to Wiskott-Aldrich Syndrome from a Family

Wang,

Zhang,

et al. 2024

International Journal of Genomics

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Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive genetic disease characterized by clinical symptoms such as eczema, thrombocytopenia with small platelets, immune deficiency, prone to autoimmune diseases, and malignant tumors. This disease is caused by mutations of the WAS gene encoding WASprotein (WASP). The locus and type of mutations of the WAS gene and the expression quantity of WASP were strongly correlated with the clinical manifestations of patients. We found a novel mutation in the WAS gene (c.931+5G>C), which affected splicing to produce three abnormal mRNA, resulting in an abnormally truncated WASP. This mutation led to a reduction but not the elimination of the normal WASP population, resulting in causes X-linked thrombocytopenia (XLT) with mild clinical manifestations. Our findings revealed the pathogenic mechanism of this mutation.

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“…This phenotype can be explained by exon skipping or intron retention (Inoue et al, 2004). Splicing sites affected by mutations have been described for many pathological phenotypes: neurofibromatosis type 1 (Jang et al, 2016), familial hypercholesterolemia (Shakhtshneider et al, 2017), Wiskott-Aldrich syndrome and chronic colitis (Esmaeilzadeh et al, 2018), hypophosphatemic rickets (Ma et al, 2015), and others. Mutations affecting splicing have been found not only in canonical splicing sites but also in introns and exons and may have a tissue-specific effect, as in familial dysautonomia (Slaugenhaupt et al, 2001;Abramowicz, Gos, 2018).…”

Section: Discussionmentioning

confidence: 99%

A rare splice site mutation in the gene encoding glucokinase/hexokinase 4 in a patient with MODY type 2

et al. 2020

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The article presents a variant of maturity onset diabetes of the young type 2, caused by a rare mutation in the GCK gene. Maturity onset diabetes of the young (MODY) is a hereditary form of diabetes with an autosomal dominant type of inheritance, an onset at a young age, and a primary defect in pancreatic β-cell function. This type of diabetes is different from classical types of diabetes mellitus (DM1 and DM2) in its clinical course, treatment strategies, and prognosis. Clinical manifestations of MODY are heterogeneous and may vary even among members of the same family, i. e., carriers of identical mutations. This phenotypic variation is due to the interaction of mutations with different genetic backgrounds and the influence of environmental factors (e. g., lifestyle). Using next-generation sequencing technology, the c.580-1G>A substitution (IVS5 -1G>A, rs1554335421) located in an acceptor splice site of intron 5 of the GCK gene was found in a proband. The identified variant cosegregated with a pathological phenotype in the examined family members. The GCK gene encodes glucokinase (hexokinase 4), which catalyzes the first step in a large number of glucose metabolic pathways such as glycolysis. Mutations in this gene are the cause of MODY2. The illness is characterized by an insignificant increase in the fasting glucose level, is a well-controlled disease without medication, and has a low prevalence of micro-and macrovascular complications of diabetes. The presented case of MODY2 reveals the clinical significance of a mutation in the splice site of the GCK gene. When nonclassical diabetes mellitus is being diagnosed in young people and pregnant women, genetic testing is needed to verify the diagnosis and to select the optimal treatment method.

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A novel splice site mutation in WAS gene in patient with Wiskott-Aldrich syndrome and chronic colitis: a case report

Cited by 6 publications

References 18 publications

A Review on Secondary Immune Thrombocytopenia in Malaysia

A Review on Secondary Immune Thrombocytopenia in Malaysia

A Novel Splicing Mutation Leading to Wiskott-Aldrich Syndrome from a Family

A rare splice site mutation in the gene encoding glucokinase/hexokinase 4 in a patient with MODY type 2

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