A family with hereditary hyperferritinaemia cataract syndrome: evidence of incomplete penetrance and clinical heterogeneity

González-Huerta, Luz María; Ramírez-Sánchez, Verónica; Rivera-Vega, M.R.; Messina-Baas, Olga; Cuevas-Covarrubias, Sergio A.

doi:10.1111/j.1365-2141.2008.07345.x

Cited by 7 publications

(4 citation statements)

References 9 publications

(9 reference statements)

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“…It is also possible that the dominance/recessivity of CRYBB3 alleles can be modified by secondary factors, consistent with the incomplete penetrance of the dominant c.581T>A, p.(Val194Glu) allele reported in this manuscript. Incomplete penetrance has been associated with mutations in several other autosomal dominant cataract genes: GJA8 (He et al 2011), FTL (Gonzalez-Huerta et al 2008), GJA3 (Burdon et al 2004), CRYGC (Ren et al 2000), and CRYAB (Sacconi et al 2012). …”

Section: Resultsmentioning

confidence: 99%

Whole exome sequencing in dominant cataract identifies a new causative factor, CRYBA2, and a variety of novel alleles in known genes

et al. 2013

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Pediatric cataracts are observed in 1–15 per 10,000 births with 10–25% of cases attributed to genetic causes; autosomal dominant inheritance is the most commonly observed pattern. Since the specific cataract phenotype is not sufficient to predict which gene is mutated, whole exome sequencing (WES) was utilized to concurrently screen all known cataract genes and to examine novel candidate factors for a disease-causing mutation in probands from 23 pedigrees affected with familial dominant cataract. Review of WES data for 36 known cataract genes identified causative mutations in nine pedigrees (39%) in CRYAA, CRYBB1, CRYBB3, CRYGC (2), CRYGD, GJA8 (2), and MIP and an additional likely causative mutation in EYA1; the CRYBB3 mutation represents the first dominant allele in this gene and demonstrates incomplete penetrance. Examination of crystallin genes not yet linked to human disease identified a novel cataract gene, CRYBA2, a member of the βγ-crystallin superfamily. The p.(Val50Met) mutation in CRYBA2 cosegregated with disease phenotype in a four-generation pedigree with autosomal dominant congenital cataracts with incomplete penetrance. Expression studies detected cryba2 transcripts during early lens development in zebrafish, supporting its role in congenital disease. Our data highlight the extreme genetic heterogeneity of dominant cataract as the eleven causative/likely causative mutations affected nine different genes and the majority of mutant alleles were novel. Furthermore, these data suggest that less than half of dominant cataract can be explained by mutations in currently known genes.

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Section: Resultsmentioning

confidence: 99%

Whole exome sequencing in dominant cataract identifies a new causative factor, CRYBA2, and a variety of novel alleles in known genes

et al. 2013

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“…No variants (or copy number variations) in syndactyly genes were identified in the index patient (II:1) with the BCOR variant nor in the patient’s aunt (I:3). Thus, patient II:1 could have the foot anomaly as part of OFCD syndrome that shows syndactyly or camptodactyly as a common feature . However, the genetic cause for the syndactyly in patient I:3 remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Genetic Analysis in a Swiss Cohort of Bilateral Congenital Cataract

et al. 2021

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population-based differences in genotype and phenotype heterogeneity are important for targeted and patient-specific diagnosis and treatment, counseling, and screening strategies.OBJECTIVE To report disease-causing variants and their detailed phenotype in patients with bilateral congenital cataract from a single center in Switzerland and thereby draw a genetic map and perform a genotype-phenotype comparison of this cohort.DESIGN, SETTING, AND PARTICIPANTS This clinical and molecular-genetic cohort study took place through the collaboration of the

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“…Moreover, several authors have related the penetrance and severity of cataracts to the IRE region where the mutation is located [4,7]. Due to the variability in the age at onset of cataracts, different levels of ferritin and different degrees of severity of cataracts may be observed within the same family [8,12].…”

Section: Discussionmentioning

confidence: 99%

The hereditary hyperferritinemia–cataract syndrome: a family study

Álvarez-Coca-González

Moreno-Carralero

Martínez-Pérez

et al. 2010

Eur J Pediatr

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Ferritin is an acute-phase reactant that is elevated in the course of infectious, inflammatory, autoimmune, and oncological diseases and the hemophagocytic syndrome. In asymptomatic patients, isolated hyperferritinemia may be due to different causes depending on whether or not it is accompanied by iron overload. Hyperferritinemia values above 300 ng/ml and an excess of body iron levels may be indicative of hemochromatosis. However, if such values develop in the absence of iron overload, they may be secondary to hemochromatosis type 4a (ferroportin disease) or more often to hereditary hyperferritinemia-cataract syndrome (HHCS; Aguilar-Martinez et al., Am J Gastroenterol 100:1185-1194, 2005; Ferrante et al., Eur J Gastroenterol Hepatol 17:1247-1253, 2005). HHCS results from different mutations in the L-ferritin gene (FTL) on chromosome 19 (19q13.1), causing autosomal dominant transmission (Bertola et al., Curr Drug Targets Immune Endocr Metabol Disord 4:93-105, 2004). We present a child with HHCS due to the allelic variant c.-167C>T (C33T) in the iron-responsive element region of the FTL gene. When pediatricians encounter an asymptomatic patient with isolated hyperferritinemia in the absence of iron overload, they should consider the possibility of HHCS, especially if other members of the family have developed cataracts from a young age.

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A family with hereditary hyperferritinaemia cataract syndrome: evidence of incomplete penetrance and clinical heterogeneity

Cited by 7 publications

References 9 publications

Whole exome sequencing in dominant cataract identifies a new causative factor, CRYBA2, and a variety of novel alleles in known genes

Whole exome sequencing in dominant cataract identifies a new causative factor, CRYBA2, and a variety of novel alleles in known genes

Genetic Analysis in a Swiss Cohort of Bilateral Congenital Cataract

The hereditary hyperferritinemia–cataract syndrome: a family study

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