Limb disorders

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. Limb abnormalities were reported in all 3 pedigrees. 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, 10:49 a.m. | Last Modified: 23 Feb 2026, 10:49 a.m.

Panel Version: 7.17

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: 7.16

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Fanconi anemia, complementation group X, OMIM:621258

Publications

• 40232843
• 40244696