Cytopenia - NOT Fanconi anaemia

Gene: FASLG

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance updated to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 10 Dec 2025, 3:27 p.m. | Last Modified: 10 Dec 2025, 3:27 p.m.

Panel Version: 4.30

Comment on list classification: There is sufficient evidence available for the association of both monoallelic and biallelic FASLG variants with ALPS, which has cytopenia as presenting phenotype. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 19 Jun 2025, 12:31 p.m. | Last Modified: 19 Jun 2025, 12:31 p.m.

Panel Version: 4.9

Patients with monoallelic variants:

PMID:8787672 - A 64-year-old African American male patient with systemic lupus erythematosus with lymphadenopathy was identified with a heterozygous 84bp deletion within exon 4 of FASLG that results in a in-frame deletion. The patient displayed leukopenia.

PMID:17605793 - A 20-year-old male patient of European descent was reported with generalised lymphadenopathy and splenomegaly since 18 months of age. He developed thrombocytopenia, neutropenia and anemia at age three. The patient, his father and paternal grandmother were identified with a heterozygous A530G variant in FASLG gene. The patient's father had lymphadenopathy as an adolescent and was healthy otherwise except for psoriatic arthritis. The grandmother was not reported with any symptoms of autoimmune lymphoproliferative syndrome (ALPS). An unrelated 13-year-old female patient of European descent was diagnosed with thrombocytopenia with positive anti-platelet antibodies at 3 years of age during hospitalisation for septic arthritis and was identified with A320G variant in FASLG.

Patients with biallelic variants:

PMID:16627752 - A Spanish patient with ALPS was identified with a homozygous missense variant in FASL (A247E). The healthy mother was heterozygous for the variant. DNA from the father was not available. The patient presented with both autoimmune thrombopenia and haemolytic anaemia.

PMID:25451160 - Two siblings from a Libyan family who presented with a severe phenotype of ALPS was identified with a homozygous 1 bp insertion predicted to result in a frameshift and a truncated protein (p.P69Afs*75). The healthy mother was heterozygous for the variant. One of these brothers had thrombocytopenia.

PMID:26334989 - Two Moroccan brothers with a severe form of ALPS were identified with a novel homozygous FASLG variant (G605C). These brothers had both thrombocytopenia and anaemia.

Monoallelic FASLG variants are associated with ALPS phenotype in OMIM (MIM #601859), but biallelic variants are not associated with any phenotypes. OMIM also reports autoimmune hemolytic anemia, thrombocytopenia and neutropenia as clinical presentations of ALPS.

Created: 19 Jun 2025, 12:29 p.m. | Last Modified: 19 Jun 2025, 12:29 p.m.

Panel Version: 4.5

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
Autoimmune lymphoproliferative syndrome, type IB, OMIM:601859

Publications

• 8787672
• 16627752
• 17605793
• 25451160
• 26334989

Green List (high evidence)

FASLG pathogenic variants (germline or somatic) causes ALPS, which has a complex phenotype including different cytopenias (mostly autoimmune).
Sources: Other

Created: 13 Oct 2024, 9:01 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
ALPS