Mutation spectrum and clinical investigation of achromatopsia patients with mutations in the GNAT2 gene

Julia Felden; Britta Baumann; Manir Ali; Isabelle Audo; Carmen Ayuso; Beatrice Bocquet; Ingele Casteels; Blanca Garcia-Sandoval; Samuel G Jacobson; Bernhard Jurklies; Ulrich Kellner; Line Kessel; Birgit Lorenz; Martin McKibbin; Isabelle Meunier; Thomy de Ravel; Thomas Rosenberg; Klaus Rüther; Maria Vadala; Bernd Wissinger; Katarina Stingl; Susanne Kohl

doi:10.1002/humu.23768

Mutation spectrum and clinical investigation of achromatopsia patients with mutations in the GNAT2 gene

Julia Felden, Britta Baumann, Manir Ali, Isabelle Audo, Carmen Ayuso, Beatrice Bocquet, Ingele Casteels, Blanca Garcia-Sandoval, Samuel G Jacobson, Bernhard Jurklies, Ulrich Kellner, Line Kessel, Birgit Lorenz, Martin McKibbin, Isabelle Meunier, Thomy de Ravel, Thomas Rosenberg, Klaus Rüther, Maria Vadala, Bernd WissingerKatarina Stingl, Susanne Kohl

Institut for Klinisk Medicin

6 Citationer (Scopus)

Abstract

Achromatopsia (ACHM) is a hereditary cone photoreceptor disorder characterized by the inability to discriminate colors, nystagmus, photophobia, and low-visual acuity. Six genes have been associated with this rare autosomal recessively inherited disease, including the GNAT2 gene encoding the catalytic α-subunit of the G-protein transducin which is expressed in the cone photoreceptor outer segment. Out of a cohort of 1,116 independent families diagnosed with a primary clinical diagnosis of ACHM, we identified 23 patients with ACHM from 19 independent families with likely causative mutations in GNAT2, representing 1.7% of our large ACHM cohort. In total 22 different potentially disease-causing variants, of which 12 are novel, were identified. The mutation spectrum also includes a novel copy number variation, a heterozygous duplication of exon 4, of which the breakpoint matches exactly that of the previously reported exon 4 deletion. Two patients carry just a single heterozygous variant. In addition to our previous study on GNAT2-ACHM, we also present detailed clinical data of these patients.

Originalsprog	Engelsk
Tidsskrift	Human Mutation
Vol/bind	40
Udgave nummer	8
Sider (fra-til)	1145-1155
Antal sider	11
ISSN	1059-7794
DOI	https://doi.org/10.1002/humu.23768
Status	Udgivet - 2019

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10.1002/humu.23768

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Felden, J., Baumann, B., Ali, M., Audo, I., Ayuso, C., Bocquet, B., Casteels, I., Garcia-Sandoval, B., Jacobson, S. G., Jurklies, B., Kellner, U., Kessel, L., Lorenz, B., McKibbin, M., Meunier, I., de Ravel, T., Rosenberg, T., Rüther, K., Vadala, M., ... Kohl, S. (2019). Mutation spectrum and clinical investigation of achromatopsia patients with mutations in the GNAT2 gene. Human Mutation, 40(8), 1145-1155. https://doi.org/10.1002/humu.23768

Felden, J, Baumann, B, Ali, M, Audo, I, Ayuso, C, Bocquet, B, Casteels, I, Garcia-Sandoval, B, Jacobson, SG, Jurklies, B, Kellner, U, Kessel, L, Lorenz, B, McKibbin, M, Meunier, I, de Ravel, T, Rosenberg, T, Rüther, K, Vadala, M, Wissinger, B, Stingl, K & Kohl, S 2019, 'Mutation spectrum and clinical investigation of achromatopsia patients with mutations in the GNAT2 gene', Human Mutation, bind 40, nr. 8, s. 1145-1155. https://doi.org/10.1002/humu.23768

@article{6c04ee35fbc44865abd91f6f3bcf4dba,

title = "Mutation spectrum and clinical investigation of achromatopsia patients with mutations in the GNAT2 gene",

abstract = "Achromatopsia (ACHM) is a hereditary cone photoreceptor disorder characterized by the inability to discriminate colors, nystagmus, photophobia, and low-visual acuity. Six genes have been associated with this rare autosomal recessively inherited disease, including the GNAT2 gene encoding the catalytic α-subunit of the G-protein transducin which is expressed in the cone photoreceptor outer segment. Out of a cohort of 1,116 independent families diagnosed with a primary clinical diagnosis of ACHM, we identified 23 patients with ACHM from 19 independent families with likely causative mutations in GNAT2, representing 1.7% of our large ACHM cohort. In total 22 different potentially disease-causing variants, of which 12 are novel, were identified. The mutation spectrum also includes a novel copy number variation, a heterozygous duplication of exon 4, of which the breakpoint matches exactly that of the previously reported exon 4 deletion. Two patients carry just a single heterozygous variant. In addition to our previous study on GNAT2-ACHM, we also present detailed clinical data of these patients.",

author = "Julia Felden and Britta Baumann and Manir Ali and Isabelle Audo and Carmen Ayuso and Beatrice Bocquet and Ingele Casteels and Blanca Garcia-Sandoval and Jacobson, {Samuel G} and Bernhard Jurklies and Ulrich Kellner and Line Kessel and Birgit Lorenz and Martin McKibbin and Isabelle Meunier and {de Ravel}, Thomy and Thomas Rosenberg and Klaus R{\"u}ther and Maria Vadala and Bernd Wissinger and Katarina Stingl and Susanne Kohl",

year = "2019",

doi = "10.1002/humu.23768",

language = "English",

volume = "40",

pages = "1145--1155",

journal = "Human Mutation",

issn = "1059-7794",

publisher = "JohnWiley & Sons, Inc.",

number = "8",

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TY - JOUR

T1 - Mutation spectrum and clinical investigation of achromatopsia patients with mutations in the GNAT2 gene

AU - Felden, Julia

AU - Baumann, Britta

AU - Ali, Manir

AU - Audo, Isabelle

AU - Ayuso, Carmen

AU - Bocquet, Beatrice

AU - Casteels, Ingele

AU - Garcia-Sandoval, Blanca

AU - Jacobson, Samuel G

AU - Jurklies, Bernhard

AU - Kellner, Ulrich

AU - Kessel, Line

AU - Lorenz, Birgit

AU - McKibbin, Martin

AU - Meunier, Isabelle

AU - de Ravel, Thomy

AU - Rosenberg, Thomas

AU - Rüther, Klaus

AU - Vadala, Maria

AU - Wissinger, Bernd

AU - Stingl, Katarina

AU - Kohl, Susanne

PY - 2019

Y1 - 2019

N2 - Achromatopsia (ACHM) is a hereditary cone photoreceptor disorder characterized by the inability to discriminate colors, nystagmus, photophobia, and low-visual acuity. Six genes have been associated with this rare autosomal recessively inherited disease, including the GNAT2 gene encoding the catalytic α-subunit of the G-protein transducin which is expressed in the cone photoreceptor outer segment. Out of a cohort of 1,116 independent families diagnosed with a primary clinical diagnosis of ACHM, we identified 23 patients with ACHM from 19 independent families with likely causative mutations in GNAT2, representing 1.7% of our large ACHM cohort. In total 22 different potentially disease-causing variants, of which 12 are novel, were identified. The mutation spectrum also includes a novel copy number variation, a heterozygous duplication of exon 4, of which the breakpoint matches exactly that of the previously reported exon 4 deletion. Two patients carry just a single heterozygous variant. In addition to our previous study on GNAT2-ACHM, we also present detailed clinical data of these patients.

AB - Achromatopsia (ACHM) is a hereditary cone photoreceptor disorder characterized by the inability to discriminate colors, nystagmus, photophobia, and low-visual acuity. Six genes have been associated with this rare autosomal recessively inherited disease, including the GNAT2 gene encoding the catalytic α-subunit of the G-protein transducin which is expressed in the cone photoreceptor outer segment. Out of a cohort of 1,116 independent families diagnosed with a primary clinical diagnosis of ACHM, we identified 23 patients with ACHM from 19 independent families with likely causative mutations in GNAT2, representing 1.7% of our large ACHM cohort. In total 22 different potentially disease-causing variants, of which 12 are novel, were identified. The mutation spectrum also includes a novel copy number variation, a heterozygous duplication of exon 4, of which the breakpoint matches exactly that of the previously reported exon 4 deletion. Two patients carry just a single heterozygous variant. In addition to our previous study on GNAT2-ACHM, we also present detailed clinical data of these patients.

U2 - 10.1002/humu.23768

DO - 10.1002/humu.23768

M3 - Journal article

C2 - 31058429

SN - 1059-7794

VL - 40

SP - 1145

EP - 1155

JO - Human Mutation

JF - Human Mutation

IS - 8

ER -

Mutation spectrum and clinical investigation of achromatopsia patients with mutations in the GNAT2 gene

Abstract

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