Clinical and genetic profiles of patients with X-linked agammaglobulinemia from southeast Turkey: Novel mutations in BTK gene

Doğruel, Dilek; Serbes, Mahir; Şaşihüseyinoğlu, Ayşe Şenay; Yılmaz, M.; Altıntaş, Derya Ufuk; Bişgin, Atıl

doi:10.1016/j.aller.2018.03.004

Cited by 8 publications

(7 citation statements)

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“…In a previously reported single center series on XLA from Chandigarh, arthritis was observed in 42% patients. Joint involvement in patients with XLA in present series was observed to be higher than that reported from United States, Argentina, Italy and Iran ( 24 , 26 , 28 , 30 ) but similar to that reported from Hong Kong (29%) ( 31 , 37 ), Mexico (38%) ( 35 ), Africa (37%), Turkey (22%) ( 27 ) and China (22%) ( 29 ) ( Table 3 ). It has been observed that patients with XLA who fail to maintain adequate trough levels despite IVIg replacement therapy are at higher risk of developing arthritis.…”

Section: Discussionsupporting

confidence: 88%

“…In our previous study we had reported a mean delay of 4.2 years Delays in diagnosis are primarily a reflection of lack of awareness about PIDs among medical professionals as well as the laity. Diagnostic delays of upto several years have been noted in series from Latin America, Africa and the Middle East ( 24 – 27 ) ( Table 3 ). However, a greater delay in the diagnosis was noted in our scenario ( 20 ) emphasizing the need for concerted efforts to shorten this delay.…”

Section: Discussionmentioning

confidence: 99%

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Clinical and Genetic Profile of X-Linked Agammaglobulinemia: A Multicenter Experience From India

et al. 2021

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BackgroundThere is paucity of literature on XLA from developing countries. Herein we report the clinical and molecular profile and outcome in a multicenter cohort of patients with XLA from India.MethodsData on XLA from all regional centers supported by the Foundation for Primary Immunodeficiency Diseases (FPID), USA and other institutions providing care to patients with PIDs were collated. Diagnosis of XLA was based on European Society for Immunodeficiencies (ESID) criteria.ResultsWe received clinical details of 195 patients with a provisional diagnosis of XLA from 12 centers. At final analysis, 145 patients were included (137 ‘definite XLA’ and eight ‘probable/possible XLA’). Median age at onset of symptoms was 12.0 (6.0, 36.0) months and median age at diagnosis was 60.0 (31.5, 108) months. Pneumonia was the commonest clinical manifestation (82.6%) followed by otitis media (50%) and diarrhea (42%). Arthritis was seen in 26% patients while 23% patients developed meningitis. Bronchiectasis was seen in 10% and encephalitis (likely viral) in 4.8% patients. Pseudomonas aeruginosa was the commonest bacterial pathogen identified followed by Streptococcus pneumoniae, Staphylococcus aureus and Klebsiella pneumoniae. Molecular analysis revealed 86 variants in 105 unrelated cases. Missense variants in BTK gene were the most common (36%) followed by frameshift (22%) and nonsense variants (21%). Most pathogenic gene variants (53%) were clustered in the distal part of gene encompassing exons 14–19 encoding for the tyrosine kinase domain. Follow-up details were available for 108 patients. Of these, 12% had died till the time of this analysis. The 5-year and 10-year survival was 89.9% and 86.9% respectively. Median duration of follow-up was 61 months and total duration of follow-up was 6083.2 patient-months. All patients received intravenous immunoglobulin (IVIg) replacement therapy. However, in many patients IVIg could not be given at recommended doses or intervals due to difficulties in accessing this therapy because of financial reasons and lack of universal health insurance in India. Hematopoietic stem cell transplant was carried out in four (2.8%) patients.ConclusionThere was a significant delay in the diagnosis and facilities for molecular diagnosis were not available at many centers. Optimal immunoglobulin replacement is still a challenge

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Clinical and Genetic Profile of X-Linked Agammaglobulinemia: A Multicenter Experience From India

et al. 2021

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“…The tyrosine 545 is highly conserved (Figure ). The c.974 + 5G > A and c.179_181del (p.Lys60del) were previously described 25,26 …”

Section: Resultsmentioning

confidence: 99%

Phenotypic heterogeneity and genotypic spectrum of inborn errors of immunity identified through whole exome sequencing in a Thai patient cohort

Tengsujaritkul

Suratannon

Ittiwut

et al. 2021

Pediatric Allergy Immunology

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Background Inborn errors of immunity (IEI) comprise more than 400 rare diseases with potential life‐threatening conditions. Clinical manifestations and genetic defects are heterogeneous and diverse among populations. Here, we aimed to characterize the clinical, immunologic, and genetic features of Thai pediatric patients with IEI. The use of whole‐exome sequencing (WES) in diagnosis and clinical decision making was also assessed. Methods Thirty six unrelated patients with clinical and laboratory findings consistent with IEI were recruited from January 2010 to December 2020. WES was performed to identify the underlying genetic defects. Results The median age of disease onset was 4 months (range: 1 month to 13 years), and 24 were male (66.7%). Recurrent sinopulmonary tract infection was the most common clinical presentation followed by septicemia and severe pneumonia. Using WES, we successfully identified the underlying genetic defects in 18 patients (50%). Of the 20 variants identified, six have not been previously described (30%). According to the International Union of Immunological Societies (IUIS), 38.9% of these detected cases (7/18) were found to harbor variants associated with genes in combined immunodeficiencies with associated or syndromic features (Class II). Conclusion The diagnostic yield of WES in this patient cohort was 50%. Six novel genetic variants in IEI genes were identified. The clinical usefulness of WES in IEI was demonstrated, emphasizing it as an effective diagnostic strategy in these genetically heterogeneous disorders.

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“…27 BTK tiene un papel crucial en la maduración de las células pre-B a células B maduras. 28 La función principal de esta proteína es promover la expansión de células pre-B en la etapa de pre-B1 a pre-B2. 29 Como resultado de la mutación en el gen BTK hay falla en el desarrollo de las células B y los pacientes afectados tienen niveles reducidos (< 1 %) de linfocitos B maduros XLA se hereda de forma vinculada al cromosoma X; BTK es el único gen conocido que lo causa.…”

Section: Agammaglobulinemia Ligada a Xunclassified

Conceptos generales de las inmunodeficiencias humorales

Velásquez-Ortiz

O’Farrill-Romanillos

Ruiz

2020

RAM

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Las inmunodeficiencias humorales (IDH) comprenden un grupo de enfermedades caracterizadas por la imposibilidad de desarrollar una respuesta inmune efectiva mediada por inmunoglobulinas. Los pacientes con IDH presentan infecciones por bacterias extracelulares encapsuladas, principalmente en el tracto respiratorio o gastrointestinal y una mayor predisposición a padecer enfermedades autoinmunes y cáncer. Algunas se originan por defectos genéticos bien definidos y en otras se desconoce la causa. Las manifestaciones clínicas de algunas IDH pueden ser tardías y el diagnóstico se apoya en pruebas de laboratorio como la concentración en suero de las inmunoglobulinas, determinación de poblaciones linfocitarias y estudios funcionales. El tratamiento de reemplazo con gammaglobulinas disminuye significativamente las infecciones graves. Para lograr un diagnóstico temprano es necesario un alto índice de sospecha y evaluar las manifestaciones clínicas y de laboratorio sugestivas de IDH. Las tecnologías de secuenciación masiva han favorecido la descripción de mutaciones en varios genes que llevan a un fenotipo clínico de IDH, con lo que se abre el camino para comprender mejor las inmunopatologías en las IDH.

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Clinical and genetic profiles of patients with X-linked agammaglobulinemia from southeast Turkey: Novel mutations in BTK gene

Abstract: Our results show that mutations in southeast Turkey could be different from those in the rest of the world and molecular genetic tests are an important tool for early confirmed diagnosis of XLA.

Cited by 8 publications

References 28 publications

Clinical and Genetic Profile of X-Linked Agammaglobulinemia: A Multicenter Experience From India

Clinical and Genetic Profile of X-Linked Agammaglobulinemia: A Multicenter Experience From India

Phenotypic heterogeneity and genotypic spectrum of inborn errors of immunity identified through whole exome sequencing in a Thai patient cohort

Conceptos generales de las inmunodeficiencias humorales

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