schliessen

Filtern

 

Bibliotheken

Mutation of ATF6 causes autosomal recessive achromatopsia

Achromatopsia (ACHM) is an early-onset retinal dystrophy characterized by photophobia, nystagmus, color blindness and severely reduced visual acuity. Currently mutations in five genes CNGA3 , CNGB3 , GNAT2 , PDE6C and PDE6H have been implicated in ACHM. We performed homozygosity mapping and linkage... Full description

Journal Title: Human Genetics 2015, Vol.134(9), pp.941-950
Main Author: Ansar, Muhammad
Other Authors: Santos-Cortez, Regie , Saqib, Muhammad , Zulfiqar, Fareeha , Lee, Kwanghyuk , Ashraf, Naeem , Ullah, Ehsan , Wang, Xin , Sajid, Sundus , Khan, Falak , Amin-ud-Din, Muhammad , Smith, Joshua , Shendure, Jay , Bamshad, Michael , Nickerson, Deborah , Hameed, Abdul , Riazuddin, Saima , Ahmed, Zubair , Ahmad, Wasim , Leal, Suzanne
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0340-6717 ; E-ISSN: 1432-1203 ; DOI: 10.1007/s00439-015-1571-4
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: springer_jour10.1007/s00439-015-1571-4
title: Mutation of ATF6 causes autosomal recessive achromatopsia
format: Article
creator:
  • Ansar, Muhammad
  • Santos-Cortez, Regie
  • Saqib, Muhammad
  • Zulfiqar, Fareeha
  • Lee, Kwanghyuk
  • Ashraf, Naeem
  • Ullah, Ehsan
  • Wang, Xin
  • Sajid, Sundus
  • Khan, Falak
  • Amin-ud-Din, Muhammad
  • Smith, Joshua
  • Shendure, Jay
  • Bamshad, Michael
  • Nickerson, Deborah
  • Hameed, Abdul
  • Riazuddin, Saima
  • Ahmed, Zubair
  • Ahmad, Wasim
  • Leal, Suzanne
subjects:
  • Color Blindness -- Genetic Aspects
  • Protein Binding
ispartof: Human Genetics, 2015, Vol.134(9), pp.941-950
description: Achromatopsia (ACHM) is an early-onset retinal dystrophy characterized by photophobia, nystagmus, color blindness and severely reduced visual acuity. Currently mutations in five genes CNGA3 , CNGB3 , GNAT2 , PDE6C and PDE6H have been implicated in ACHM. We performed homozygosity mapping and linkage analysis in a consanguineous Pakistani ACHM family and mapped the locus to a 15.12-Mb region on chromosome 1q23.1–q24.3 with a maximum LOD score of 3.6. A DNA sample from an affected family member underwent exome sequencing. Within the ATF6 gene, a single-base insertion variant c.355_356dupG (p.Glu119Glyfs*8) was identified, which completely segregates with the ACHM phenotype within the family. The frameshift variant was absent in public variant databases, in 130 exomes from unrelated Pakistani individuals, and in 235 ethnically matched controls. The variant is predicted to result in a truncated protein that lacks the DNA binding and transmembrane domains and therefore affects the function of ATF6 as a transcription factor that initiates the unfolded protein response during endoplasmic reticulum (ER) stress. Immunolabeling with anti-ATF6 antibodies showed localization throughout the mouse neuronal retina, including retinal pigment epithelium, photoreceptor cells, inner nuclear layer, inner and outer plexiform layers, with a more prominent signal in retinal ganglion cells. In contrast to cytoplasmic expression of wild-type protein, in heterologous cells ATF6 protein with the p.Glu119Glyfs*8 variant is mainly confined to the nucleus. Our results imply that response to ER stress as mediated by the ATF6 pathway is essential for color vision in humans.
language: eng
source:
identifier: ISSN: 0340-6717 ; E-ISSN: 1432-1203 ; DOI: 10.1007/s00439-015-1571-4
fulltext: fulltext_linktorsrc
issn:
  • 1432-1203
  • 14321203
  • 0340-6717
  • 03406717
url: Link


@attributes
ID1208800783
RANK0.07
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
LOCALfalse
PrimoNMBib
record
control
sourcerecordid10.1007/s00439-015-1571-4
sourceidspringer_jour
recordidTN_springer_jour10.1007/s00439-015-1571-4
sourcesystemPC
pqid1702654046
galeid424660876
display
typearticle
titleMutation of ATF6 causes autosomal recessive achromatopsia
creatorAnsar, Muhammad ; Santos-Cortez, Regie ; Saqib, Muhammad ; Zulfiqar, Fareeha ; Lee, Kwanghyuk ; Ashraf, Naeem ; Ullah, Ehsan ; Wang, Xin ; Sajid, Sundus ; Khan, Falak ; Amin-ud-Din, Muhammad ; Smith, Joshua ; Shendure, Jay ; Bamshad, Michael ; Nickerson, Deborah ; Hameed, Abdul ; Riazuddin, Saima ; Ahmed, Zubair ; Ahmad, Wasim ; Leal, Suzanne
ispartofHuman Genetics, 2015, Vol.134(9), pp.941-950
identifier
descriptionAchromatopsia (ACHM) is an early-onset retinal dystrophy characterized by photophobia, nystagmus, color blindness and severely reduced visual acuity. Currently mutations in five genes CNGA3 , CNGB3 , GNAT2 , PDE6C and PDE6H have been implicated in ACHM. We performed homozygosity mapping and linkage analysis in a consanguineous Pakistani ACHM family and mapped the locus to a 15.12-Mb region on chromosome 1q23.1–q24.3 with a maximum LOD score of 3.6. A DNA sample from an affected family member underwent exome sequencing. Within the ATF6 gene, a single-base insertion variant c.355_356dupG (p.Glu119Glyfs*8) was identified, which completely segregates with the ACHM phenotype within the family. The frameshift variant was absent in public variant databases, in 130 exomes from unrelated Pakistani individuals, and in 235 ethnically matched controls. The variant is predicted to result in a truncated protein that lacks the DNA binding and transmembrane domains and therefore affects the function of ATF6 as a transcription factor that initiates the unfolded protein response during endoplasmic reticulum (ER) stress. Immunolabeling with anti-ATF6 antibodies showed localization throughout the mouse neuronal retina, including retinal pigment epithelium, photoreceptor cells, inner nuclear layer, inner and outer plexiform layers, with a more prominent signal in retinal ganglion cells. In contrast to cytoplasmic expression of wild-type protein, in heterologous cells ATF6 protein with the p.Glu119Glyfs*8 variant is mainly confined to the nucleus. Our results imply that response to ER stress as mediated by the ATF6 pathway is essential for color vision in humans.
languageeng
source
subjectColor Blindness -- Genetic Aspects ; Protein Binding;
version8
oafree_for_read
lds50peer_reviewed
links
openurl$$Topenurl_article
linktorsrc$$Uhttp://dx.doi.org/10.1007/s00439-015-1571-4$$EView_full_text_in_Springer
openurlfulltext$$Topenurlfull_article
search
creatorcontrib
0Ansar, Muhammad, Lyn
1Santos-Cortez, Regie, Arif
2Saqib, Muhammad, Mahmood
3Zulfiqar, Fareeha, Sher
4Lee, Kwanghyuk, D.
5Ashraf, Naeem, J.
6Ullah, Ehsan, A.
7Wang, Xin, M.
8Sajid, Sundus, M.
9Khan, Falak, M.
10Amin-ud-Din, Muhammad, M.
11Smith, Joshua, M.
12Shendure, Jay, M.
13Bamshad, Michael, M.
14Nickerson, Deborah, M.
15Hameed, Abdul, M.
16Riazuddin, Saima, M.
17Ahmed, Zubair, M.
18Ahmad, Wasim, M.
19Leal, Suzanne, M.
titleMutation of ATF6 causes autosomal recessive achromatopsia
descriptionAchromatopsia (ACHM) is an early-onset retinal dystrophy characterized by photophobia, nystagmus, color blindness and severely reduced visual acuity. Currently mutations in five genes CNGA3 , CNGB3 , GNAT2 , PDE6C and PDE6H have been implicated in ACHM. We performed homozygosity mapping and linkage analysis in a consanguineous Pakistani ACHM family and mapped the locus to a 15.12-Mb region on chromosome 1q23.1–q24.3 with a maximum LOD score of 3.6. A DNA sample from an affected family member underwent exome sequencing. Within the ATF6 gene, a single-base insertion variant c.355_356dupG (p.Glu119Glyfs*8) was identified, which completely segregates with the ACHM phenotype within the family. The frameshift variant was absent in public variant databases, in 130 exomes from unrelated Pakistani individuals, and in 235 ethnically matched controls. The variant is predicted to result in a truncated protein that lacks the DNA binding and transmembrane domains and therefore affects the function of ATF6 as a transcription factor that initiates the unfolded protein response during endoplasmic reticulum (ER) stress. Immunolabeling with anti-ATF6 antibodies showed localization throughout the mouse neuronal retina, including retinal pigment epithelium, photoreceptor cells, inner nuclear layer, inner and outer plexiform layers, with a more prominent signal in retinal ganglion cells. In contrast to cytoplasmic expression of wild-type protein, in heterologous cells ATF6 protein with the p.Glu119Glyfs*8 variant is mainly confined to the nucleus. Our results imply that response to ER stress as mediated by the ATF6 pathway is essential for color vision in humans.
general
010.1007/s00439-015-1571-4
1English
2Springer Science & Business Media B.V.
3SpringerLink Open Access
sourceidspringer_jour
recordidspringer_jour10.1007/s00439-015-1571-4
issn
01432-1203
114321203
20340-6717
303406717
rsrctypearticle
creationdate2015
addtitle
0Human Genetics
1Hum Genet
searchscopespringer_free
scopespringer_free
lsr30VSR-Enriched:[galeid, subject, pqid, pages]
sort
titleMutation of ATF6 causes autosomal recessive achromatopsia
authorAnsar, Muhammad ; Santos-Cortez, Regie ; Saqib, Muhammad ; Zulfiqar, Fareeha ; Lee, Kwanghyuk ; Ashraf, Naeem ; Ullah, Ehsan ; Wang, Xin ; Sajid, Sundus ; Khan, Falak ; Amin-ud-Din, Muhammad ; Smith, Joshua ; Shendure, Jay ; Bamshad, Michael ; Nickerson, Deborah ; Hameed, Abdul ; Riazuddin, Saima ; Ahmed, Zubair ; Ahmad, Wasim ; Leal, Suzanne
creationdate20150900
facets
frbrgroupid3730085757911406150
frbrtype5
languageeng
creationdate2015
collectionSpringerLink Open Access
prefilterarticles
rsrctypearticles
creatorcontrib
0Ansar, Muhammad
1Santos-Cortez, Regie
2Saqib, Muhammad
3Zulfiqar, Fareeha
4Lee, Kwanghyuk
5Ashraf, Naeem
6Ullah, Ehsan
7Wang, Xin
8Sajid, Sundus
9Khan, Falak
10Amin-ud-Din, Muhammad
11Smith, Joshua
12Shendure, Jay
13Bamshad, Michael
14Nickerson, Deborah
15Hameed, Abdul
16Riazuddin, Saima
17Ahmed, Zubair
18Ahmad, Wasim
19Leal, Suzanne
jtitleHuman Genetics
toplevelpeer_reviewed
delivery
delcategoryRemote Search Resource
fulltextfulltext_linktorsrc
addata
aulast
0Ansar
1Santos-Cortez
2Saqib
3Zulfiqar
4Lee
5Ashraf
6Ullah
7Wang
8Sajid
9Khan
10Amin-ud-Din
11Smith
12Shendure
13Bamshad
14Nickerson
15Hameed
16Riazuddin
17Ahmed
18Ahmad
19Leal
aufirst
0Muhammad
1Regie
2Lyn
3P.
4Arif
5Nadeem
6Fareeha
7Kwanghyuk
8Naeem
9Mahmood
10Ehsan
11Xin
12Sundus
13Falak
14Sher
15Joshua
16D.
17Jay
18Michael
19J.
20Deborah
21A.
22Abdul
23Saima
24Zubair
25M.
26Wasim
27Suzanne
au
0Ansar, Muhammad
1Santos-Cortez, Regie
2Saqib, Muhammad
3Zulfiqar, Fareeha
4Lee, Kwanghyuk
5Ashraf, Naeem
6Ullah, Ehsan
7Wang, Xin
8Sajid, Sundus
9Khan, Falak
10Amin-ud-Din, Muhammad
11Smith, Joshua
12Shendure, Jay
13Bamshad, Michael
14Nickerson, Deborah
15Hameed, Abdul
16Riazuddin, Saima
17Ahmed, Zubair
18Ahmad, Wasim
19Leal, Suzanne
atitleMutation of ATF6 causes autosomal recessive achromatopsia
jtitleHuman Genetics
stitleHum Genet
risdate201509
volume134
issue9
spage941
epage950
issn0340-6717
eissn1432-1203
genrearticle
ristypeJOUR
abstractAchromatopsia (ACHM) is an early-onset retinal dystrophy characterized by photophobia, nystagmus, color blindness and severely reduced visual acuity. Currently mutations in five genes CNGA3 , CNGB3 , GNAT2 , PDE6C and PDE6H have been implicated in ACHM. We performed homozygosity mapping and linkage analysis in a consanguineous Pakistani ACHM family and mapped the locus to a 15.12-Mb region on chromosome 1q23.1–q24.3 with a maximum LOD score of 3.6. A DNA sample from an affected family member underwent exome sequencing. Within the ATF6 gene, a single-base insertion variant c.355_356dupG (p.Glu119Glyfs*8) was identified, which completely segregates with the ACHM phenotype within the family. The frameshift variant was absent in public variant databases, in 130 exomes from unrelated Pakistani individuals, and in 235 ethnically matched controls. The variant is predicted to result in a truncated protein that lacks the DNA binding and transmembrane domains and therefore affects the function of ATF6 as a transcription factor that initiates the unfolded protein response during endoplasmic reticulum (ER) stress. Immunolabeling with anti-ATF6 antibodies showed localization throughout the mouse neuronal retina, including retinal pigment epithelium, photoreceptor cells, inner nuclear layer, inner and outer plexiform layers, with a more prominent signal in retinal ganglion cells. In contrast to cytoplasmic expression of wild-type protein, in heterologous cells ATF6 protein with the p.Glu119Glyfs*8 variant is mainly confined to the nucleus. Our results imply that response to ER stress as mediated by the ATF6 pathway is essential for color vision in humans.
copBerlin/Heidelberg
pubSpringer Berlin Heidelberg
doi10.1007/s00439-015-1571-4
pages941-950
oafree_for_read
date2015-09