Sutural cataract associated with a mutation in the ferritin light chain gene (FTL) in a family of Indian origin

Vanita Vanita, James Fielding Hejtmancik, Hans Christian Hennies, Kamlesh Guleria, Peter Nünberg, Daljit Singh, James Sperling, Jai Rup Singh

Research output: Contribution to journalArticle

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Abstract

Purpose: The molecular characterization of 27 members of an Indian family, with 13 members in four generations, affected with Y-sutural congenital cataract. Methods: Detailed family history and clinical data were collected. A genome-wide scan by two-point linkage analysis using more than 400 microsatellite markers in combination with multipoint lod score and haplotype analysis was performed. Mutation screening was carried out in the candidate gene by bi-directional sequencing of amplified products. Results: A maximum two-point lod score of 6.37 at θ=0.00 was obtained with marker D19S879. Haplotype analysis placed the cataract locus to a 5.0 cM region between D19S902 and D19S867, in close proximity to the L-ferritin light chain gene (FTL) on chromosome 19q13.3. Hematological tests in two affected individuals showed very high levels of serum ferritin without iron overload leading to the diagnosis of hyperferritinemia-cataract syndrome. Mutation screening in FTL identified a G>A change at position 32 (c.-168G>A) in a highly conserved 3 nucleotide motif that forms a loop structure in the iron responsive element (IRE) in the 5′-untranslated region (5′-UTR). This nucleotide alteration was neither seen in any unaffected member of the family nor found in 50 unrelated control subjects. Conclusions: The present study is the first report of a Y-sutural congenital cataract mapping to 19q13.3. The mutation observed in FTL in this family highlights the phenotypic heterogeneity of the disorder in relation to the genotype as the identical mutation (32 G>A) has previously been reported in two Italian families with entirely different phenotypes. It is also the first report of hereditary hyperferritinemia-cataract syndrome in a family of Indian origin.

LanguageEnglish
Pages93-99
Number of pages7
JournalMolecular Vision
Volume12
Publication statusPublished - 21 Feb 2006
Externally publishedYes

Fingerprint

Apoferritins
Cataract
Mutation
Genes
Lod Score
Haplotypes
Nucleotide Motifs
Iron Overload
5' Untranslated Regions
Hematologic Tests
Ferritins
Microsatellite Repeats
Nucleotides
Iron
Chromosomes
Genotype
Genome
Phenotype
Serum

Cite this

Vanita, V., Hejtmancik, J. F., Hennies, H. C., Guleria, K., Nünberg, P., Singh, D., ... Singh, J. R. (2006). Sutural cataract associated with a mutation in the ferritin light chain gene (FTL) in a family of Indian origin. Molecular Vision, 12, 93-99.
Vanita, Vanita ; Hejtmancik, James Fielding ; Hennies, Hans Christian ; Guleria, Kamlesh ; Nünberg, Peter ; Singh, Daljit ; Sperling, James ; Singh, Jai Rup. / Sutural cataract associated with a mutation in the ferritin light chain gene (FTL) in a family of Indian origin. In: Molecular Vision. 2006 ; Vol. 12. pp. 93-99.
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abstract = "Purpose: The molecular characterization of 27 members of an Indian family, with 13 members in four generations, affected with Y-sutural congenital cataract. Methods: Detailed family history and clinical data were collected. A genome-wide scan by two-point linkage analysis using more than 400 microsatellite markers in combination with multipoint lod score and haplotype analysis was performed. Mutation screening was carried out in the candidate gene by bi-directional sequencing of amplified products. Results: A maximum two-point lod score of 6.37 at θ=0.00 was obtained with marker D19S879. Haplotype analysis placed the cataract locus to a 5.0 cM region between D19S902 and D19S867, in close proximity to the L-ferritin light chain gene (FTL) on chromosome 19q13.3. Hematological tests in two affected individuals showed very high levels of serum ferritin without iron overload leading to the diagnosis of hyperferritinemia-cataract syndrome. Mutation screening in FTL identified a G>A change at position 32 (c.-168G>A) in a highly conserved 3 nucleotide motif that forms a loop structure in the iron responsive element (IRE) in the 5′-untranslated region (5′-UTR). This nucleotide alteration was neither seen in any unaffected member of the family nor found in 50 unrelated control subjects. Conclusions: The present study is the first report of a Y-sutural congenital cataract mapping to 19q13.3. The mutation observed in FTL in this family highlights the phenotypic heterogeneity of the disorder in relation to the genotype as the identical mutation (32 G>A) has previously been reported in two Italian families with entirely different phenotypes. It is also the first report of hereditary hyperferritinemia-cataract syndrome in a family of Indian origin.",
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Vanita, V, Hejtmancik, JF, Hennies, HC, Guleria, K, Nünberg, P, Singh, D, Sperling, J & Singh, JR 2006, 'Sutural cataract associated with a mutation in the ferritin light chain gene (FTL) in a family of Indian origin', Molecular Vision, vol. 12, pp. 93-99.

Sutural cataract associated with a mutation in the ferritin light chain gene (FTL) in a family of Indian origin. / Vanita, Vanita; Hejtmancik, James Fielding; Hennies, Hans Christian; Guleria, Kamlesh; Nünberg, Peter; Singh, Daljit; Sperling, James; Singh, Jai Rup.

In: Molecular Vision, Vol. 12, 21.02.2006, p. 93-99.

Research output: Contribution to journalArticle

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T1 - Sutural cataract associated with a mutation in the ferritin light chain gene (FTL) in a family of Indian origin

AU - Vanita, Vanita

AU - Hejtmancik, James Fielding

AU - Hennies, Hans Christian

AU - Guleria, Kamlesh

AU - Nünberg, Peter

AU - Singh, Daljit

AU - Sperling, James

AU - Singh, Jai Rup

PY - 2006/2/21

Y1 - 2006/2/21

N2 - Purpose: The molecular characterization of 27 members of an Indian family, with 13 members in four generations, affected with Y-sutural congenital cataract. Methods: Detailed family history and clinical data were collected. A genome-wide scan by two-point linkage analysis using more than 400 microsatellite markers in combination with multipoint lod score and haplotype analysis was performed. Mutation screening was carried out in the candidate gene by bi-directional sequencing of amplified products. Results: A maximum two-point lod score of 6.37 at θ=0.00 was obtained with marker D19S879. Haplotype analysis placed the cataract locus to a 5.0 cM region between D19S902 and D19S867, in close proximity to the L-ferritin light chain gene (FTL) on chromosome 19q13.3. Hematological tests in two affected individuals showed very high levels of serum ferritin without iron overload leading to the diagnosis of hyperferritinemia-cataract syndrome. Mutation screening in FTL identified a G>A change at position 32 (c.-168G>A) in a highly conserved 3 nucleotide motif that forms a loop structure in the iron responsive element (IRE) in the 5′-untranslated region (5′-UTR). This nucleotide alteration was neither seen in any unaffected member of the family nor found in 50 unrelated control subjects. Conclusions: The present study is the first report of a Y-sutural congenital cataract mapping to 19q13.3. The mutation observed in FTL in this family highlights the phenotypic heterogeneity of the disorder in relation to the genotype as the identical mutation (32 G>A) has previously been reported in two Italian families with entirely different phenotypes. It is also the first report of hereditary hyperferritinemia-cataract syndrome in a family of Indian origin.

AB - Purpose: The molecular characterization of 27 members of an Indian family, with 13 members in four generations, affected with Y-sutural congenital cataract. Methods: Detailed family history and clinical data were collected. A genome-wide scan by two-point linkage analysis using more than 400 microsatellite markers in combination with multipoint lod score and haplotype analysis was performed. Mutation screening was carried out in the candidate gene by bi-directional sequencing of amplified products. Results: A maximum two-point lod score of 6.37 at θ=0.00 was obtained with marker D19S879. Haplotype analysis placed the cataract locus to a 5.0 cM region between D19S902 and D19S867, in close proximity to the L-ferritin light chain gene (FTL) on chromosome 19q13.3. Hematological tests in two affected individuals showed very high levels of serum ferritin without iron overload leading to the diagnosis of hyperferritinemia-cataract syndrome. Mutation screening in FTL identified a G>A change at position 32 (c.-168G>A) in a highly conserved 3 nucleotide motif that forms a loop structure in the iron responsive element (IRE) in the 5′-untranslated region (5′-UTR). This nucleotide alteration was neither seen in any unaffected member of the family nor found in 50 unrelated control subjects. Conclusions: The present study is the first report of a Y-sutural congenital cataract mapping to 19q13.3. The mutation observed in FTL in this family highlights the phenotypic heterogeneity of the disorder in relation to the genotype as the identical mutation (32 G>A) has previously been reported in two Italian families with entirely different phenotypes. It is also the first report of hereditary hyperferritinemia-cataract syndrome in a family of Indian origin.

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