Positive diepoxybutane test in a patient with Nijmegen Breakage Syndrome

Gallego, Marta S.; Barreiro, Cristina; Danielian, Silvia; Rosenweig, S.D.

doi:10.1002/pbc.20941

Cited by 3 publications

(3 citation statements)

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“…Reaction to alkylating agents has been tested in cells from some patients, but results are equivocal with both insensitivity [43,44,48] and moderate hypersensitivity [39,50,51,134-136] reported. A positive DEB test contributed to misdiagnosis of NBS as FA in one family, and as a consequence bone marrow transplantation was performed.…”

Section: Diagnosis Diagnostic Criteria and Methodsmentioning

confidence: 99%

Nijmegen breakage syndrome (NBS)

Chrzanowska

Gregorek

Dembowska‐Bagińska

et al. 2012

Orphanet J Rare Dis

214

185

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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 naw...

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Section: Diagnosis Diagnostic Criteria and Methodsmentioning

confidence: 99%

Nijmegen breakage syndrome (NBS)

Chrzanowska

Gregorek

Dembowska‐Bagińska

et al. 2012

Orphanet J Rare Dis

214

185

View full text Add to dashboard Cite

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“…We read with interest the letter by Gallego et al 2 of an abnormal DEB test in a patient with NBS which appears in this issue of Pediatric Blood & Cancer . In contrast to the two families with NBS and abnormal DEB tests described by ourselves and Gennery et al 3,4 this girl has the common NBS mutation (675del5) and a typical phenotype, demonstrating that an abnormal DEB test may be found in patients with a variety of NBS mutations and differing disease phenotypes.…”

mentioning

confidence: 99%

The utility of the diepoxybutane test in Nijmegen breakage syndrome diagnosis

Cale

New

2007

Pediatric Blood & Cancer

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“…Reaction to alkylating agents has been tested in cells from some patients, but results are equivocal with both insensitivity [43,44,48] and moderate hypersensitivity [39,50,51,[134][135][136] reported. A positive DEB test contributed to misdiagnosis of NBS as FA in one family, and as a consequence bone marrow transplantation was performed.…”

Section: Induced Chromosomal Instabilitymentioning

confidence: 99%

Nijmegen Breakage Syndrome (NBS)

SpringerReference

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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...

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Positive diepoxybutane test in a patient with Nijmegen Breakage Syndrome

Cited by 3 publications

References 3 publications

Nijmegen breakage syndrome (NBS)

Nijmegen breakage syndrome (NBS)

The utility of the diepoxybutane test in Nijmegen breakage syndrome diagnosis

Nijmegen Breakage Syndrome (NBS)

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