Somatic loss of heterozygosity, but not haploinsufficiency alone, leads to full-blown autoimmune lymphoproliferative syndrome in 1 of 12 family members with FAS start codon mutation.
Clin Immunol
; 147(1): 61-68, 2013 Apr.
Article
em En
| MEDLINE
| ID: mdl-23524443
ABSTRACT
We describe a family with 12 members carrying a heterozygous germline FAS c.3G>T start codon mutation leading to FAS haploinsufficiency. One patient had autoimmune lymphoproliferative syndrome (ALPS), one had recovered from ALPS, and ten mutation-positive relatives (MPRs) were healthy. FAS-mediated apoptosis and surface expression of FAS in single-positive T cells were lower for MPRs but did not discriminate between them and the ALPS patient. However, double-negative (DN) T cells of the ALPS patient had no FAS expression due to somatic loss of heterozygosity. Our results in this kindred suggest that FAS haploinsufficiency does not cause ALPS-FAS, but that modifying genetic events are crucial for its pathogenesis. FAS surface expression on DN T cells should be assessed routinely and FAS haploinsufficient patients should be followed as its potential for lymphomagenesis is not well defined and a second hit might occur later on.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Códon de Iniciação
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Receptor fas
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Perda de Heterozigosidade
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Síndrome Linfoproliferativa Autoimune
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Mutação
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article