Mutation spectrum of the FZD-4, TSPAN12 AND ZNF408 genes in Indian FEVR patients
Identifieur interne : 000D70 ( Main/Exploration ); précédent : 000D69; suivant : 000D71Mutation spectrum of the FZD-4, TSPAN12 AND ZNF408 genes in Indian FEVR patients
Auteurs : Ganeswara Rao Musada [Inde] ; Hameed Syed [Inde] ; Subhadra Jalali [Inde] ; Subhabrata Chakrabarti [Inde] ; Inderjeet Kaur [Inde]Source :
- BMC Ophthalmology [ 1471-2415 ] ; 2016.
Abstract
Mutations in candidate genes that encode for a ligand (
The DNA of 110 unrelated FEVR patients and 115 unaffected controls were screened for variations in the entire coding and untranslated regions of these 3 genes by resequencing. Segregation of the disease-associated variants was assessed in the family members of the probands. The effect of the observed missense changes were further analyzed by SIFT and PolyPhen-2 scores.
The screening of
Our genetic screening revealed varying mutation frequencies in the
The online version of this article (doi:10.1186/s12886-016-0236-y) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s12886-016-0236-y
PubMed: 27316669
PubMed Central: 4912735
Affiliations:
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Kanuri Santhamma Centre for Vitreo Retinal Diseases, LV Prasad Eye Institute, Hyderabad, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Smt. 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Kanuri Santhamma Centre for Vitreo Retinal Diseases, LV Prasad Eye Institute, Hyderabad, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Smt. Kanuri Santhamma Centre for Vitreo Retinal Diseases, LV Prasad Eye Institute, Hyderabad</wicri:regionArea><wicri:noRegion>Hyderabad</wicri:noRegion></affiliation></author><author><name sortKey="Chakrabarti, Subhabrata" sort="Chakrabarti, Subhabrata" uniqKey="Chakrabarti S" first="Subhabrata" last="Chakrabarti">Subhabrata Chakrabarti</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Kallam Anji Reddy Molecular Genetics Laboratory, Brien Holden Eye Research Centre, L V Prasad Eye Institute (KAR Campus), Road#2, Banjara Hills, Hyderabad, 500034 India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Kallam Anji Reddy Molecular Genetics Laboratory, Brien Holden Eye Research Centre, L V Prasad Eye Institute (KAR Campus), Road#2, Banjara Hills, Hyderabad</wicri:regionArea><wicri:noRegion>Hyderabad</wicri:noRegion></affiliation></author><author><name sortKey="Kaur, Inderjeet" sort="Kaur, Inderjeet" uniqKey="Kaur I" first="Inderjeet" last="Kaur">Inderjeet Kaur</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Kallam Anji Reddy Molecular Genetics Laboratory, Brien Holden Eye Research Centre, L V Prasad Eye Institute (KAR Campus), Road#2, Banjara Hills, Hyderabad, 500034 India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Kallam Anji Reddy Molecular Genetics Laboratory, Brien Holden Eye Research Centre, L V Prasad Eye Institute (KAR Campus), Road#2, Banjara Hills, Hyderabad</wicri:regionArea><wicri:noRegion>Hyderabad</wicri:noRegion></affiliation></author></analytic><series><title level="j">BMC Ophthalmology</title><idno type="eISSN">1471-2415</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Mutations in candidate genes that encode for a ligand (<italic>NDP</italic>) and receptor complex (<italic>FZD4, LRP5 and TSPAN12</italic>) in the Norrin β-catenin signaling pathway are involved in the pathogenesis of familial exudative vitreoretinopathy (FEVR, MIM # 133780). Recently, a transcription factor (<italic>ZNF408</italic>) has also been implicated in FEVR. We had earlier characterized the variations in <italic>NDP</italic> among FEVR patients from India. The present study aimed at understanding the involvement of the remaining genes (<italic>FZD4</italic>, <italic>TSPAN12</italic> and <italic>ZNF408</italic>) in the same cohort.</p></sec><sec><title>Methods</title><p>The DNA of 110 unrelated FEVR patients and 115 unaffected controls were screened for variations in the entire coding and untranslated regions of these 3 genes by resequencing. Segregation of the disease-associated variants was assessed in the family members of the probands. The effect of the observed missense changes were further analyzed by SIFT and PolyPhen-2 scores.</p></sec><sec><title>Results</title><p>The screening of <italic>FZD4, TSPAN12</italic> and <italic>ZNF408</italic> genes identified 11 different mutations in 15/110 FEVR probands. Of the 11 identified mutations, 6 mutations were novel. The detected missense mutations were mainly located in the domains which are functionally crucial for the formation of ligand-receptor complex and as they replaced evolutionarily highly conserved amino acids with a SIFT score < 0.005, they are predicted to be pathogenic. Additionally 2 novel and 16 reported single nucleotide polymorphisms (SNP) were also detected.</p></sec><sec><title>Conclusions</title><p>Our genetic screening revealed varying mutation frequencies in the <italic>FZD4</italic> (8.0 %)<italic>, TSPAN12</italic> (5.4 %) and <italic>ZNF408</italic> (2.7 %) genes among the FEVR patients, indicating their potential role in the disease pathogenesis. The observed mutations segregated with the disease phenotype and exhibited variable expressivity. The mutations in <italic>FZD4</italic> and <italic>TSPAN12</italic> were involved in autosomal dominant and autosomal recessive families and further validates the involvement of these gene in FEVR development.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1186/s12886-016-0236-y) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Salvo, J" uniqKey="Salvo J">J Salvo</name></author><author><name sortKey="Lyubasyuk, V" uniqKey="Lyubasyuk V">V Lyubasyuk</name></author><author><name sortKey="Xu, M" uniqKey="Xu M">M Xu</name></author><author><name sortKey="Wang, H" uniqKey="Wang H">H Wang</name></author><author><name sortKey="Wang, F" uniqKey="Wang F">F Wang</name></author><author><name sortKey="Nguyen, D" uniqKey="Nguyen D">D Nguyen</name></author><author><name sortKey="Wang, K" uniqKey="Wang K">K 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uniqKey="Hujeirat Y">Y Hujeirat</name></author><author><name sortKey="Khayat, M" uniqKey="Khayat M">M Khayat</name></author><author><name sortKey="Pe R, J" uniqKey="Pe R J">J Pe’er</name></author><author><name sortKey="Shalev, S" uniqKey="Shalev S">S Shalev</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kondo, H" uniqKey="Kondo H">H Kondo</name></author><author><name sortKey="Qin, M" uniqKey="Qin M">M Qin</name></author><author><name sortKey="Tahira, T" uniqKey="Tahira T">T Tahira</name></author><author><name sortKey="Uchio, E" uniqKey="Uchio E">E Uchio</name></author><author><name sortKey="Hayashi, K" uniqKey="Hayashi K">K Hayashi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Boucheix, C" uniqKey="Boucheix C">C Boucheix</name></author><author><name sortKey="Rubinstein, E" uniqKey="Rubinstein E">E Rubinstein</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Inde</li></country></list><tree><country name="Inde"><noRegion><name sortKey="Musada, Ganeswara Rao" sort="Musada, Ganeswara Rao" uniqKey="Musada G" first="Ganeswara Rao" last="Musada">Ganeswara Rao Musada</name></noRegion><name sortKey="Chakrabarti, Subhabrata" sort="Chakrabarti, Subhabrata" uniqKey="Chakrabarti S" first="Subhabrata" last="Chakrabarti">Subhabrata Chakrabarti</name><name sortKey="Jalali, Subhadra" sort="Jalali, Subhadra" uniqKey="Jalali S" first="Subhadra" last="Jalali">Subhadra Jalali</name><name sortKey="Kaur, Inderjeet" sort="Kaur, Inderjeet" uniqKey="Kaur I" first="Inderjeet" last="Kaur">Inderjeet Kaur</name><name sortKey="Syed, Hameed" sort="Syed, Hameed" uniqKey="Syed H" first="Hameed" last="Syed">Hameed Syed</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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