van der Burg M, de Groot R, Comans-Bitter W M, den Hollander J C, Hooijkaas H, Neijens H J, Berger R M, Oranje A P, Langerak A W, van Dongen J J
Department of Immunology, Erasmus University Rotterdam, The Netherlands.
Pediatr Res. 2000 Mar;47(3):336-43. doi: 10.1203/00006450-200003000-00009.
Autoimmune lymphoproliferative syndrome (ALPS) is characterized by autoimmune features and lymphoproliferations and is generally caused by defective Fas-mediated apoptosis. This report describes a child with clinical features of ALPS without detectable Fas expression on freshly isolated blood leukocytes. Detection of FAS transcripts via real-time quantitative PCR made a severe transcriptional defect unlikely. Sequencing of the FAS gene revealed a 20-nucleotide duplication in the last exon affecting the cytoplasmic signaling domain. The patient was homozygous for this mutation, whereas the consanguineous parents and the siblings were heterozygous. The patient reported here is a human homologue of the Fas-null mouse, inasmuch as she carries an autosomal homozygous mutation in the FAS gene and she shows the severe and accelerated ALPS phenotype. The heterozygous family members did not have the ALPS phenotype, indicating that the disease-causing FAS mutation in this family is autosomal recessive.
自身免疫性淋巴细胞增生综合征（ALPS）的特征为自身免疫特征和淋巴细胞增生，通常由Fas介导的凋亡缺陷引起。本报告描述了一名具有ALPS临床特征的儿童，其新鲜分离的血液白细胞上未检测到Fas表达。通过实时定量PCR检测FAS转录本，排除了严重转录缺陷的可能性。FAS基因测序显示最后一个外显子中有20个核苷酸重复，影响细胞质信号结构域。该患者对此突变呈纯合状态，而近亲父母和兄弟姐妹为杂合子。此处报告的患者是Fas基因缺失小鼠的人类同源物，因为她在FAS基因中携带常染色体纯合突变，并且表现出严重且加速的ALPS表型。杂合的家庭成员没有ALPS表型，表明该家族中导致疾病的FAS突变是常染色体隐性的。
