INTRODUCTION: X-linked agammagobulinemia (XLA) is a primary immunodeficiency disorder caused by Bruton's tyrosine kinase (Btk) gene mutation. Recent studies suggested genotype-phenotype correlation in XLA, but a definitive association remains controversial. PATIENTS AND METHODS: We examined the relationship between specific Btk gene mutations and severity of clinical presentation in 62 patients with XLA. Disease severity was assessed by the age of disease onset and the presence of severe infections, while mutations were classified into severe and mild based on structural and functional consequence by bioinformatics analysis. RESULTS: Fifty-six Btk mutations were identified in 62 patients from 57 kindreds. Variation in phenotypes was observed, and there was a tendency of association between genotype and age of disease onset as well as occurrence of severe infections. CONCLUSION: A critical analysis of the circumstances upon presentation also revealed that under-recognition of recurrent infections and relevant family history are important hurdles to timely diagnosis of XLA.
INTRODUCTION:X-linked agammagobulinemia (XLA) is a primary immunodeficiency disorder caused by Bruton's tyrosine kinase (Btk) gene mutation. Recent studies suggested genotype-phenotype correlation in XLA, but a definitive association remains controversial. PATIENTS AND METHODS: We examined the relationship between specific Btk gene mutations and severity of clinical presentation in 62 patients with XLA. Disease severity was assessed by the age of disease onset and the presence of severe infections, while mutations were classified into severe and mild based on structural and functional consequence by bioinformatics analysis. RESULTS: Fifty-six Btk mutations were identified in 62 patients from 57 kindreds. Variation in phenotypes was observed, and there was a tendency of association between genotype and age of disease onset as well as occurrence of severe infections. CONCLUSION: A critical analysis of the circumstances upon presentation also revealed that under-recognition of recurrent infections and relevant family history are important hurdles to timely diagnosis of XLA.
Authors: E Baraldi; K Djinovic Carugo; M Hyvönen; P L Surdo; A M Riley; B V Potter; R O'Brien; J E Ladbury; M Saraste Journal: Structure Date: 1999-04-15 Impact factor: 5.006
Authors: Jessica M Lindvall; K Emelie M Blomberg; Jouni Väliaho; Leonardo Vargas; Juhana E Heinonen; Anna Berglöf; Abdalla J Mohamed; Beston F Nore; Mauno Vihinen; C I Edvard Smith Journal: Immunol Rev Date: 2005-02 Impact factor: 12.988
Authors: E Holinski-Feder; M Weiss; O Brandau; K B Jedele; B Nore; C M Bäckesjö; M Vihinen; S R Hubbard; B H Belohradsky; C I Smith; A Meindl Journal: Pediatrics Date: 1998-02 Impact factor: 7.124
Authors: D J Rawlings; D C Saffran; S Tsukada; D A Largaespada; J C Grimaldi; L Cohen; R N Mohr; J F Bazan; M Howard; N G Copeland Journal: Science Date: 1993-07-16 Impact factor: 47.728
Authors: D Vetrie; I Vorechovský; P Sideras; J Holland; A Davies; F Flinter; L Hammarström; C Kinnon; R Levinsky; M Bobrow Journal: Nature Date: 1993-01-21 Impact factor: 49.962
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