Bilateral congenital or childhood onset cataracts

Gene: FTL

Green List (high evidence)

Comment on mode of inheritance: There are 2 unrelated cases reported with biallelic FTL variants and cataracts (1 case with onset at 35yrs, and 2 sibs with cataract onset at 17 & 20 yrs). As only 1 case matches the panel scope of childhood-onset, the MOI should remain as MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown, until more evidence emerges.

Created: 4 Jun 2026, 10:11 a.m. | Last Modified: 4 Jun 2026, 10:11 a.m.

Panel Version: 8.1

Reports of BIALLELIC cases:
PMID: 32241646 Ciftciler, Yılmaz & Buyukasik, 2020
Report of two sisters with FTL c.473T > C; p.Pro158Leu and unmeasurable serum ferritin levels, but normal on other iron measurements, no clinical symptoms apart from fatigue. 2 affected sibs were homozygous for the variant, unaffected parents and sister were heterozygous. No cataracts or neurological symptoms reported.

PMID: 23940258 Cozzi et al., 2013
Report of a 23-yr-old female patient affected by a homozygous variant in FTL: c.310G>T, p.(E104X); presented with idiopathic generalized seizures, and atypical restless leg syndrome (RLS). There was no FTL expression in patient fibroblasts - confirmed LoF. Increased iron incorporation, cytosolic iron deficiency, and oxidative damage were also seen in patient fibroblast experiments. No mention of cataracts

PMID: 23300176 Giansily-Blaizot et al., 2013
Proband = 54yo female with unexplained hyperferritinemia (initially 1960 μg/L), developed microcytic anemia; bilateral cataract diagnosed at age 35 yrs; she harboured a homozygous FTL variant NM_000146.3: c.-149G>C (+51G>C). Diagnosis of Hereditary hyperferritinemia cataract syndrome (HHCS). Family history of cataracts / visual impairment, but not sequenced.
The same variant "G51C" found previously in father-child pairs in a heterozygous state in PMID: 10759702 and PMID: 11704046. 1 allele reported in gnomAD v4.1.1.

PMID: 23421845 Luscieti et al., 2013
FTL mutations reported in 2 HHCS pedigrees: "Badalona" +36C>U - NM_000146.3: c.-164C > T (found in both het and homozygous state) and the "Heidelberg" +52G>C mutation - NM_000146.3]; c.-148 G > C. Cataracts were diagnosed at 16-27yrs in these families.
"Badalona" +36C>U has 1 allele reported and "Heidelberg" +52G>C is not reported in gnomAD v4.1.1.

Created: 4 Jun 2026, 9:49 a.m. | Last Modified: 4 Jun 2026, 10:07 a.m.

Panel Version: 8.1

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hyperferritinemia-cataract syndrome, OMIM:600886; L-ferritin deficiency, dominant and recessive, OMIM:615604

Publications

• 23300176
• 23421845
• 23940258
• 32241646

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Hyperferritinemia-cataract syndrome, 600886; Hyperferritinemia Cataract Syndrome

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

It is on the on the Manchester congenital cataracts gene panel. A confirmed DD gene for HEREDITARY HYPERFERRITINEMIA-CATARACT SYNDROME. Associated with Hyperferritinemia-cataract syndrome in OMIM.

Created: 22 Apr 2016, 5:10 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
HEREDITARY HYPERFERRITINEMIA-CATARACT SYNDROME