Genetic and Developmental Disorders: Genetic Disorders |

Genetic Analysis of Familial X-Linked Agammaglobulinemia FREE TO VIEW

Wei Guan; Duchao Zhang; Peng Yan; Kun Xiao; Hongjun Gu; Lixin Xie
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Chinese PLA General Hospital, Beijing, China

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;149(4_S):A250. doi:10.1016/j.chest.2016.02.260
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SESSION TITLE: Genetic Disorders

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM

PURPOSE: X-linked agammaglobulinemia (XLA) is a rare inherited disease characterized by an arrest of B cell differentiation, leading to recurrent bacterial infections. Mutation of Bruton's tyrosine kinase (BTK) gene has been identified as a cause of XLA. This study aimed to explore the role of genetic factors in the XLA by pedigree genetic analysis, providing meaningful BTK gene mutation for the mechanism of XLA in Chinese population.

METHODS: We selected a case of X-linked agammaglobulinemia family from Henan Provience. The patient and his mother was analysised by the whole-exome sequencing. And then, the mutated gene was analysised by Sanger sequencing. The expression of BTK protein product detected in monocytes was tested by flow cytometry to explain whether this mutation site isassociated with XLA.

RESULTS: In this study, wefind 18 SNPsin BTK gene, including three novel SNPs. The mutated site X: 101360588, c.756G> A (p.Trp252Ter) located in SH3 domain may greatly weaken the binding capacity of SH3BP5. The exon 8, where this site is located in, was sequenced by Sanger sequencing. The flow cytometry of the blood shows that the expression of BTK protein in mononuclear cells of female carriers are different from the normal. The novel mutated site X: 101360588, c.756G> A (p.Trp252Ter) can indeed cause BTK protein product detected, therefore causing obstacles to the development of B lymphocytes and led to XLA.

CONCLUSIONS: BTK gene mutation can change the BTK protein structure and (or) function, and led to XLA. We found three novel mutations in the BTK gene by a case of Henan pedigrees. The novel mutation X: 101360588, c.756G> A (p.Trp252Ter) may cause BTK and SH3BP5 binding decline, and lead to BTK protein dysfunction and developmental disorders of B lymphocytes, which could cause XLA.

CLINICAL IMPLICATIONS: The novel mutation X: 101360588, c.756G> A (p.Trp252Ter) that we found are possibly associated with BTK protein dysfunction and developmental disorders of B lymphocytes, therefore leading to XLA. BTK mutation analysis is necessary in the diagnosis of XLA and can be used for subsequent genetic counseling, carrier detection and prenatal diagnosis.

DISCLOSURE: The following authors have nothing to disclose: Wei Guan, Duchao Zhang, Peng Yan, Kun Xiao, Hongjun Gu, Lixin Xie

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