Autoimmune lymphoproliferative syndrome (ALPS) is a rare disease characterized by defective FAS signaling, which results in chronic, nonmalignant lymphoproliferation and autoimmunity accompanied by increased risk of developing malignancies later in life.
In this, report a case of a newborn boy with a novel germline homozygous variant identified in the FAS gene, exon 9, c.775del is described, which is considered pathogenic. The consequence of this sequence change is 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 is also affected by ALPS and is 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 improves the patient clinical manifestations with obvious reduction in the percentage of DNTs.
In this report 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*) is described. Sirolimus significantly reduces DNTs and substantially relieves the patient’s clinical symptoms. Read the full article here.