Confirmed Fanconi anaemia or Bloom syndrome

Gene: FAAP100

Green List (high evidence)

Comment on list classification: 3 unrelated families have been reported in literature with biallelic FAAP100 variants and diagnosis of Fanconi anemia. Mouse and zebrafish knockout models support the association with the disease. Based on available evidence, this gene should be promoted to Green at the next update.

Created: 23 Feb 2026, 10:44 a.m. | Last Modified: 23 Feb 2026, 10:44 a.m.

Panel Version: 2.12

PMID: 40232843 Kuehl et al., 2025
Report of a consanguineous family including a fetus homozygous for FAAP100 c.1642A>C p.(T542P). Proband phenotype: growth retardation, radial ray defects, duodenal atresia, ventricular septal defect, and hydrocephalus; cellular hypersensitivity to ICL induction by mitomycin C - consistent with FA spectrum.
Functional studies: Faap100-/- mice exhibited embryonic lethality, microsomia, malformations, and gonadal atrophy resembling mice with established Fanconi anemia subtypes. Also, faap100–/– zebrafish show a complete female-to-male sex reversal, consistent with 17 other zebrafish fanc gene–KO models.

PMID: 40244696 Harrison et al., 2025
Family 1: consanguineous, presented with a history of 8 pregnancies, 6 of which resulted in spontaneous abortion and 2 that resulted in death of the infant soon after birth; liveborn children presented with severe developmental and hematologic abnormalities: prenatal ventriculomegaly, absent right kidney, IUGR, multiple limb abnormalities, and cardiac defects in 1st pregnancy; and severe IUGR, hydrocephalus, multicystic dysplastic kidneys, a contracted and hypoplastic urinary bladder, and an imperforate anus in 2nd pregnancy.
Chromosome breakage studies showed 2.94 breaks/chromosome in individual A (control = 0.06) - result consistent with Fanconi anemia.
Both sibs were homozygous for FAAP100 variant c.1151_1161del; p.E384Gfs*28; parents confirmed het.

Family 2: nonconsanguineous parents with history of 2 spontaneous abortions and a female child (individual C) that died at 14 months due to respiratory failure. Individual C presented with presented with congenital anomalies including bilateral microtia, reduced radius size in both forearms, absence of both thumbs, and a right radial club hand. Severe anomalies detected in individual D on a prenatal scan: bilateral cerebral lateral ventriculomegaly, a dysplastic pancreatic tail, bilateral ectopic kidneys, and incomplete lung lobation - pregnancy was terminated. Individual D was found to be homozygous for c.2590C>T (p.Gln864Ter). Variant is in the stretch of homozygosity, suggesting a founder effect; parents confirmed het.

FAAP100 is linked to Fanconi anemia, complementation group X, MIM:621258 (OMIM accessed 23rd Feb 2026).
Sources: Literature

Created: 23 Feb 2026, 10:42 a.m. | Last Modified: 23 Feb 2026, 10:48 a.m.

Panel Version: 2.13

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Fanconi anemia, complementation group X, OMIM:621258

Publications

• 40232843
• 40244696