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Description of a family with X-linked oculo-auriculo-vertebral spectrum associated with polyalanine tract expansion in ZIC3

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Trimouille, Aurélien ; Tingaud-Sequeira, Angèle ; Lacombe, Didier ; Duelund Hjortshøj, Tina ; Kreiborg, Sven ; Buciek Hove, Hanne ; Rooryck, Caroline. / Description of a family with X-linked oculo-auriculo-vertebral spectrum associated with polyalanine tract expansion in ZIC3. I: Clinical Genetics. 2020 ; Bind 98, Nr. 4. s. 384-389.

Bibtex

@article{d3bce6a782af46e58138eb52fe09b62c,
title = "Description of a family with X-linked oculo-auriculo-vertebral spectrum associated with polyalanine tract expansion in ZIC3",
abstract = "Oculo-auriculo-vertebral spectrum (OAVS) [MIM:164210], or Goldenhar syndrome, is a developmental disorder associating defects of structures derived from the first and second branchial arches. The genetic origin of OAVS is supported by the description of rare deleterious variants in a few causative genes, and several chromosomal copy number variations. We describe here a large family with eight male members affected by a mild form of the spectrum, mostly auricular defects, harboring a hemizygous ZIC3 variant detected by familial exome sequencing: c.159_161dup p.(Ala55dup), resulting in an expansion of the normal 10 consecutive alanine residues to 11 alanines. Segregation analysis shows its presence in all the affected individuals, with a recessive X-linked transmission. Whole-genome sequencing performed in another affected male allowed to exclude linkage disequilibrium between this ZIC3 variant and another potential pathogenic variant in this family. Furthermore, by screening of a cohort of 274 OAVS patients, we found 1 male patient carrying an expansion of 10 to 12 alanines, a variant previously reported in patient presenting with VACTERL. Loss-of-function variants of ZIC3 are causing heterotaxy or cardiac malformations. These alanine expansion variants could have a different impact on the protein and thereby resulting in a different phenotype within the OAVS/VACTERL.",
author = "Aur{\'e}lien Trimouille and Ang{\`e}le Tingaud-Sequeira and Didier Lacombe and {Duelund Hjortsh{\o}j}, Tina and Sven Kreiborg and {Buciek Hove}, Hanne and Caroline Rooryck",
note = "{\textcopyright} 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.",
year = "2020",
month = oct,
doi = "10.1111/cge.13811",
language = "English",
volume = "98",
pages = "384--389",
journal = "Clinical Genetics",
issn = "0009-9163",
publisher = "Wiley-Blackwell Munksgaard",
number = "4",

}

RIS

TY - JOUR

T1 - Description of a family with X-linked oculo-auriculo-vertebral spectrum associated with polyalanine tract expansion in ZIC3

AU - Trimouille, Aurélien

AU - Tingaud-Sequeira, Angèle

AU - Lacombe, Didier

AU - Duelund Hjortshøj, Tina

AU - Kreiborg, Sven

AU - Buciek Hove, Hanne

AU - Rooryck, Caroline

N1 - © 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.

PY - 2020/10

Y1 - 2020/10

N2 - Oculo-auriculo-vertebral spectrum (OAVS) [MIM:164210], or Goldenhar syndrome, is a developmental disorder associating defects of structures derived from the first and second branchial arches. The genetic origin of OAVS is supported by the description of rare deleterious variants in a few causative genes, and several chromosomal copy number variations. We describe here a large family with eight male members affected by a mild form of the spectrum, mostly auricular defects, harboring a hemizygous ZIC3 variant detected by familial exome sequencing: c.159_161dup p.(Ala55dup), resulting in an expansion of the normal 10 consecutive alanine residues to 11 alanines. Segregation analysis shows its presence in all the affected individuals, with a recessive X-linked transmission. Whole-genome sequencing performed in another affected male allowed to exclude linkage disequilibrium between this ZIC3 variant and another potential pathogenic variant in this family. Furthermore, by screening of a cohort of 274 OAVS patients, we found 1 male patient carrying an expansion of 10 to 12 alanines, a variant previously reported in patient presenting with VACTERL. Loss-of-function variants of ZIC3 are causing heterotaxy or cardiac malformations. These alanine expansion variants could have a different impact on the protein and thereby resulting in a different phenotype within the OAVS/VACTERL.

AB - Oculo-auriculo-vertebral spectrum (OAVS) [MIM:164210], or Goldenhar syndrome, is a developmental disorder associating defects of structures derived from the first and second branchial arches. The genetic origin of OAVS is supported by the description of rare deleterious variants in a few causative genes, and several chromosomal copy number variations. We describe here a large family with eight male members affected by a mild form of the spectrum, mostly auricular defects, harboring a hemizygous ZIC3 variant detected by familial exome sequencing: c.159_161dup p.(Ala55dup), resulting in an expansion of the normal 10 consecutive alanine residues to 11 alanines. Segregation analysis shows its presence in all the affected individuals, with a recessive X-linked transmission. Whole-genome sequencing performed in another affected male allowed to exclude linkage disequilibrium between this ZIC3 variant and another potential pathogenic variant in this family. Furthermore, by screening of a cohort of 274 OAVS patients, we found 1 male patient carrying an expansion of 10 to 12 alanines, a variant previously reported in patient presenting with VACTERL. Loss-of-function variants of ZIC3 are causing heterotaxy or cardiac malformations. These alanine expansion variants could have a different impact on the protein and thereby resulting in a different phenotype within the OAVS/VACTERL.

U2 - 10.1111/cge.13811

DO - 10.1111/cge.13811

M3 - Journal article

C2 - 32639022

VL - 98

SP - 384

EP - 389

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

IS - 4

ER -

ID: 61715022