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ABSTRACT: Background
Autoimmune lymphoproliferative syndrome (ALPS) is a rare disease characterized by defective FAS signaling, which results in chronic, nonmalignant lymphoproliferation and autoimmunity accompanied by increased numbers of "double-negative" T-cells (DNTs) (T-cell receptor αβ+ CD4-CD8-) and an increased risk of developing malignancies later in life.Case presentation
We herein report a case of a newborn boy with a novel germline homozygous variant identified in the FAS gene, exon 9, c.775del, which was considered pathogenic. The consequence of this sequence change was the creation of a premature translational stop signal p.(lle259*), associated with a severe clinical phenotype of ALPS-FAS. The elder brother of the proband was also affected by ALPS and has been found to have the same FAS homozygous variant associated with a severe clinical phenotype of ALPS-FAS, whereas the unaffected parents are heterozygous carriers of this variant. This new variant has not previously been described in population databases (gnomAD and ExAC) or in patients with FAS-related conditions. Treatment with sirolimus effectively improved the patient clinical manifestations with obvious reduction in the percentage of DNTs.Conclusion
We described a new ALPS-FAS clinical phenotype-associated germline FAS homozygous pathogenic variant, exon 9, c.775del, that produces a premature translational stop signal p.(lle259*). Sirolimus significantly reduced DNTs and substantially relieved the patient's clinical symptoms.
SUBMITTER: Elgharbawy FM
PROVIDER: S-EPMC10159173 | biostudies-literature | 2023
REPOSITORIES: biostudies-literature
Elgharbawy Fawzia M FM Karim Mohammed Yousuf MY Soliman Dina Sameh DS Hassan Amel Siddik AS Sudarsanan Anoop A Gad Ashraf A
Frontiers in pediatrics 20230420
<h4>Background</h4>Autoimmune lymphoproliferative syndrome (ALPS) is a rare disease characterized by defective <i>FAS</i> signaling, which results in chronic, nonmalignant lymphoproliferation and autoimmunity accompanied by increased numbers of "double-negative" T-cells (DNTs) (T-cell receptor αβ+ CD4-CD8-) and an increased risk of developing malignancies later in life.<h4>Case presentation</h4>We herein report a case of a newborn boy with a novel germline homozygous variant identified in the <i ...[more]