Cargando…

A new mutation in BFSP2 (G1091A) causes autosomal dominant congenital lamellar cataracts

PURPOSE: We sought to identify the genetic defect in a four-generation Chinese family with autosomal dominant congenital lamellar cataracts and demonstrate the functional analysis with biosoftware of a candidate gene in the family. METHODS: Family history data were recorded. Clinical and ophthalmolo...

Descripción completa

Detalles Bibliográficos
Autores principales: Ma, Xu, Li, Fei-Feng, Wang, Shu-Zhen, Gao, Chang, Zhang, Meng, Zhu, Si-Quan
Formato: Texto
Lenguaje:English
Publicado: Molecular Vision 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2573734/
https://www.ncbi.nlm.nih.gov/pubmed/18958306
_version_ 1782160280006950912
author Ma, Xu
Li, Fei-Feng
Wang, Shu-Zhen
Gao, Chang
Zhang, Meng
Zhu, Si-Quan
author_facet Ma, Xu
Li, Fei-Feng
Wang, Shu-Zhen
Gao, Chang
Zhang, Meng
Zhu, Si-Quan
author_sort Ma, Xu
collection PubMed
description PURPOSE: We sought to identify the genetic defect in a four-generation Chinese family with autosomal dominant congenital lamellar cataracts and demonstrate the functional analysis with biosoftware of a candidate gene in the family. METHODS: Family history data were recorded. Clinical and ophthalmologic examinations were performed on family members. All the members were genotyped with microsatellite markers at loci considered to be associated with cataracts. Two-point LOD scores were calculated by using the Linkage Software after genotyping. A mutation was detected by using gene-specific primers in direct sequencing. Wild type and mutant proteins were analyzed with Online Bio-Software. RESULTS: Affected members of this family had lamellar cataracts. Linkage analysis was obtained at markers D3S2322 (LOD score [Z]=7.22, recombination fraction [θ]=0.0) and D3S1541 (Z=5.42, θ=0.0). Haplotype analysis indicated that the cataract gene was closely linked to these two markers. Sequencing the beaded filament structural protein 2 (BFSP2) gene revealed a G>A transversion in exon 5, which caused a conservative substitution of Arg to His at codon 339 (P.R339H). This mutation cosegregated with the disease phenotype in all affected individuals and was not observed in the unaffected family members or in 100 normal, unrelated individuals. Bioinformatic analyses showed that a highly conserved region was located around Arg339. Data generated with Online Bio-Software revealed that the mutation altered the protein’s hydrophobicity, hydrophobic moment, and chaperone and regulation activities. CONCLUSIONS: This is the first reported case of a congenital lamellar cataract phenotype associated with the mutation of Arg339His (P.R339H) in BFSP2. It highlights the physiologic importance of the beaded filament protein and demonstrates a possible mechanism of action for the mutant gene.
format Text
id pubmed-2573734
institution National Center for Biotechnology Information
language English
publishDate 2008
publisher Molecular Vision
record_format MEDLINE/PubMed
spelling pubmed-25737342008-10-28 A new mutation in BFSP2 (G1091A) causes autosomal dominant congenital lamellar cataracts Ma, Xu Li, Fei-Feng Wang, Shu-Zhen Gao, Chang Zhang, Meng Zhu, Si-Quan Mol Vis Research Article PURPOSE: We sought to identify the genetic defect in a four-generation Chinese family with autosomal dominant congenital lamellar cataracts and demonstrate the functional analysis with biosoftware of a candidate gene in the family. METHODS: Family history data were recorded. Clinical and ophthalmologic examinations were performed on family members. All the members were genotyped with microsatellite markers at loci considered to be associated with cataracts. Two-point LOD scores were calculated by using the Linkage Software after genotyping. A mutation was detected by using gene-specific primers in direct sequencing. Wild type and mutant proteins were analyzed with Online Bio-Software. RESULTS: Affected members of this family had lamellar cataracts. Linkage analysis was obtained at markers D3S2322 (LOD score [Z]=7.22, recombination fraction [θ]=0.0) and D3S1541 (Z=5.42, θ=0.0). Haplotype analysis indicated that the cataract gene was closely linked to these two markers. Sequencing the beaded filament structural protein 2 (BFSP2) gene revealed a G>A transversion in exon 5, which caused a conservative substitution of Arg to His at codon 339 (P.R339H). This mutation cosegregated with the disease phenotype in all affected individuals and was not observed in the unaffected family members or in 100 normal, unrelated individuals. Bioinformatic analyses showed that a highly conserved region was located around Arg339. Data generated with Online Bio-Software revealed that the mutation altered the protein’s hydrophobicity, hydrophobic moment, and chaperone and regulation activities. CONCLUSIONS: This is the first reported case of a congenital lamellar cataract phenotype associated with the mutation of Arg339His (P.R339H) in BFSP2. It highlights the physiologic importance of the beaded filament protein and demonstrates a possible mechanism of action for the mutant gene. Molecular Vision 2008-10-24 /pmc/articles/PMC2573734/ /pubmed/18958306 Text en http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Ma, Xu
Li, Fei-Feng
Wang, Shu-Zhen
Gao, Chang
Zhang, Meng
Zhu, Si-Quan
A new mutation in BFSP2 (G1091A) causes autosomal dominant congenital lamellar cataracts
title A new mutation in BFSP2 (G1091A) causes autosomal dominant congenital lamellar cataracts
title_full A new mutation in BFSP2 (G1091A) causes autosomal dominant congenital lamellar cataracts
title_fullStr A new mutation in BFSP2 (G1091A) causes autosomal dominant congenital lamellar cataracts
title_full_unstemmed A new mutation in BFSP2 (G1091A) causes autosomal dominant congenital lamellar cataracts
title_short A new mutation in BFSP2 (G1091A) causes autosomal dominant congenital lamellar cataracts
title_sort new mutation in bfsp2 (g1091a) causes autosomal dominant congenital lamellar cataracts
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2573734/
https://www.ncbi.nlm.nih.gov/pubmed/18958306
work_keys_str_mv AT maxu anewmutationinbfsp2g1091acausesautosomaldominantcongenitallamellarcataracts
AT lifeifeng anewmutationinbfsp2g1091acausesautosomaldominantcongenitallamellarcataracts
AT wangshuzhen anewmutationinbfsp2g1091acausesautosomaldominantcongenitallamellarcataracts
AT gaochang anewmutationinbfsp2g1091acausesautosomaldominantcongenitallamellarcataracts
AT zhangmeng anewmutationinbfsp2g1091acausesautosomaldominantcongenitallamellarcataracts
AT zhusiquan anewmutationinbfsp2g1091acausesautosomaldominantcongenitallamellarcataracts
AT maxu newmutationinbfsp2g1091acausesautosomaldominantcongenitallamellarcataracts
AT lifeifeng newmutationinbfsp2g1091acausesautosomaldominantcongenitallamellarcataracts
AT wangshuzhen newmutationinbfsp2g1091acausesautosomaldominantcongenitallamellarcataracts
AT gaochang newmutationinbfsp2g1091acausesautosomaldominantcongenitallamellarcataracts
AT zhangmeng newmutationinbfsp2g1091acausesautosomaldominantcongenitallamellarcataracts
AT zhusiquan newmutationinbfsp2g1091acausesautosomaldominantcongenitallamellarcataracts