Heterogeneity of humoral immune abnormalities in children with Nijmegen breakage syndrome: an 8-year follow-up study in a single centre

Gregorek, Hanna; Chrzanowska, Krystyna; Michałkiewicz, Jacek; Syczewska, Małgorzata; Madaliński, K

doi:10.1046/j.1365-2249.2002.01971.x

“…Hastaların üçte biri agamaglobulinemiktir ve %60'ında da bir veya birden fazla immünglobulin (Ig) veya IgG subgrup eksikliği saptanır (8,9). Hem hücresel ve hem de humoral bağışıklıkta bozukluk nedeniyle, özellikle solunum sisteminde tekrarlayan bakteriyel ve viral enfeksiyonlar sık görülmektedir.…”

Section: Discussionunclassified

“…Buna ek olarak, hasta çocukların %75'inde B hücre sayılarında düşüklük, buna eşlik eden hümoral defektler görülür. Hastaların %25'inde normal veya artmış B hücre sayıları olabilse de, spesifik antikor yapım defektleri sıklıkla vardır (9 Nijmegen Breakage sendromu için spesifik bir tedavi yoktur. Aile ve bakıcılar, lenfoma ve diğer malignitelerin belirtileri hakkında bilgilendirilmelidir.…”

Section: Discussionunclassified

Nijmegen Breakage Sendromlu Bir Olgunun Uzun Süreli izlemi

Yüzüak¹,

Göktürk²,

Sayar³

et al. 2017

Asthma Allergy Immunol

0

View full text Add to dashboard Cite

“…In some patients, however, the absolute number of B cells may be elevated even up to 1.4-2 times over the upper limit for age, despite significant deficiency of serum immunoglobulins and/or specific antibody response [70]. This may indicate an intrinsic defect of the B cell immunoglobulin class switching process (CSR) [78][79][80][81].…”

Section: B Cell Abnormalitiesmentioning

confidence: 98%

“…The absolute number of B cells (CD19+, CD20+) is reduced in 72%-75% of NBS patients and a normal count is observed only in about 12%-18% [6,12,70,73]. In some patients, however, the absolute number of B cells may be elevated even up to 1.4-2 times over the upper limit for age, despite significant deficiency of serum immunoglobulins and/or specific antibody response [70].…”

Section: B Cell Abnormalitiesmentioning

confidence: 99%

“…The in vitro proliferative response of T lymphocytes to stimulation with phytohemagglutinin (PHA), anti-CD3 monoclonal antibodies and/or anti-TCR monoclonal antibodies, as well as B cells to stimulation with concanavalin A (Con A) is greatly reduced in most NBS patients [2,3,6,8,12,43,47,70,73,77,82,83]. In most studies, delayed hypersensitivity skin tests were negative [8,84].…”

Section: Functional Defects Of Lymphocytesmentioning

confidence: 99%

See 1 more Smart Citation

Nijmegen Breakage Syndrome (NBS)

SpringerReference

0

View full text Add to dashboard Cite

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive syndrome of chromosomal instability mainly characterized by microcephaly at birth, combined immunodeficiency and predisposition to malignancies. Due to a founder mutation in the underlying NBN gene (c.657_661del5) the disease is encountered most frequently among Slavic populations. The principal clinical manifestations of the syndrome are: microcephaly, present at birth and progressive with age, dysmorphic facial features, mild growth retardation, mild-to-moderate intellectual disability, and, in females, hypergonadotropic hypogonadism. Combined cellular and humoral immunodeficiency with recurrent sinopulmonary infections, a strong predisposition to develop malignancies (predominantly of lymphoid origin) and radiosensitivity are other integral manifestations of the syndrome. The NBN gene codes for nibrin which, as part of a DNA repair complex, plays a critical nuclear role wherever double-stranded DNA ends occur, either physiologically or as a result of mutagenic exposure. Laboratory findings include: (1) spontaneous chromosomal breakage in peripheral T lymphocytes with rearrangements preferentially involving chromosomes 7 and 14, (2) sensitivity to ionizing radiation or radiomimetics as demonstrated in vitro by cytogenetic methods or by colony survival assay, (3) radioresistant DNA synthesis, (4) biallelic hypomorphic mutations in the NBN gene, and (5) absence of full-length nibrin protein. Microcephaly and immunodeficiency are common to DNA ligase IV deficiency (LIG4 syndrome) and severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation due to NHEJ1 deficiency (NHEJ1 syndrome). In fact, NBS was most commonly confused with Fanconi anaemia and LIG4 syndrome. Genetic counselling should inform parents of an affected child of the 25% risk for further children to be affected. Prenatal molecular genetic diagnosis is possible if disease-causing mutations in both alleles of the NBN gene are known. No specific therapy is available for NBS, however, hematopoietic stem cell transplantation may be one option for some patients. Prognosis is generally poor due to the extremely high rate of malignancies. Zespół Nijmegen (Nijmegen breakage syndrome; NBS) jest rzadkim schorzeniem z wrodzoną niestabilnością chromosomową dziedziczącym się w sposób autosomalny recesywny, charakteryzującym się przede wszystkim wrodzonym małogłowiem, złożonymi niedoborami odporności i predyspozycją do rozwoju nowotworów. Choroba występuje najczęściej w populacjach słowiańskich, w których uwarunkowana jest mutacją założycielską w genie NBN (c.657_661del5). Do najważniejszych objawów zespołu zalicza się: małogłowie obecne od urodzenia i postępujące z wiekiem, charakterystyczne cechy dysmorfii twarzy, opóźnienie wzrastania, niepełnosprawność intelektualną w stopniu lekkim do umiarkowanego oraz hipogonadyzm hipogonadotropowy u dziewcząt. Na obraz choroby składają się także: niedobór odporności komórkowej i humoralnej, który jest pr...

show abstract

N ijmegen Breakage Syndrome ( NBS )

2004

Encyclopedic Dictionary of Genetics, Genomics and Proteomics

0

View full text Add to dashboard Cite

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive syndrome of chromosomal instability mainly characterized by microcephaly at birth, combined immunodeficiency and predisposition to malignancies. Due to a founder mutation in the underlying NBN gene (c.657_661del5) the disease is encountered most frequently among Slavic populations. The principal clinical manifestations of the syndrome are: microcephaly, present at birth and progressive with age, dysmorphic facial features, mild growth retardation, mild-to-moderate intellectual disability, and, in females, hypergonadotropic hypogonadism. Combined cellular and humoral immunodeficiency with recurrent sinopulmonary infections, a strong predisposition to develop malignancies (predominantly of lymphoid origin) and radiosensitivity are other integral manifestations of the syndrome. The NBN gene codes for nibrin which, as part of a DNA repair complex, plays a critical nuclear role wherever double-stranded DNA ends occur, either physiologically or as a result of mutagenic exposure. Laboratory findings include: (1) spontaneous chromosomal breakage in peripheral T lymphocytes with rearrangements preferentially involving chromosomes 7 and 14, (2) sensitivity to ionizing radiation or radiomimetics as demonstrated in vitro by cytogenetic methods or by colony survival assay, (3) radioresistant DNA synthesis, (4) biallelic hypomorphic mutations in the NBN gene, and (5) absence of full-length nibrin protein. Microcephaly and immunodeficiency are common to DNA ligase IV deficiency (LIG4 syndrome) and severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation due to NHEJ1 deficiency (NHEJ1 syndrome). In fact, NBS was most commonly confused with Fanconi anaemia and LIG4 syndrome. Genetic counselling should inform parents of an affected child of the 25% risk for further children to be affected. Prenatal molecular genetic diagnosis is possible if disease-causing mutations in both alleles of the NBN gene are known. No specific therapy is available for NBS, however, hematopoietic stem cell transplantation may be one option for some patients. Prognosis is generally poor due to the extremely high rate of malignancies. Zespół Nijmegen (Nijmegen breakage syndrome; NBS) jest rzadkim schorzeniem z wrodzoną niestabilnością chromosomową dziedziczącym się w sposób autosomalny recesywny, charakteryzującym się przede wszystkim wrodzonym małogłowiem, złożonymi niedoborami odporności i predyspozycją do rozwoju nowotworów. Choroba występuje najczęściej w populacjach słowiańskich, w których uwarunkowana jest mutacją założycielską w genie NBN (c.657_661del5). Do najważniejszych objawów zespołu zalicza się: małogłowie obecne od urodzenia i postępujące z wiekiem, charakterystyczne cechy dysmorfii twarzy, opóźnienie wzrastania, niepełnosprawność intelektualną w stopniu lekkim do umiarkowanego oraz hipogonadyzm hipogonadotropowy u dziewcząt. Na obraz choroby składają się także: niedobór odporności komórkowej i humoralnej, który jest przyczyną n...

show abstract

Heterogeneity of humoral immune abnormalities in children with Nijmegen breakage syndrome: an 8-year follow-up study in a single centre

Cited by 46 publications

References 17 publications

Nijmegen Breakage Sendromlu Bir Olgunun Uzun Süreli izlemi

Nijmegen Breakage Sendromlu Bir Olgunun Uzun Süreli izlemi

Nijmegen Breakage Syndrome (NBS)

N ijmegen Breakage Syndrome ( NBS )

Contact Info

Product

Resources

About