Phenotypic heterogeneity and mosaicism in Xia-Gibbs syndrome: Five Danish patients with novel variants in AHDC1

Soren L. Faergeman; Anders B. Bojesen; Maria Rasmussen; Naja Becher; Lotte Andreasen; Brian N. Andersen; Emilie Erbs; Dorte L. Lildballe; Jens Erik K. Nielsen; Monica Zilmer; Trine Bjørg Hammer; Mikkel Andersen; Charlotte Brasch-Andersen; Christina R. Fagerberg; Niels O. Illum; Mette B. Thorup; Pernille A. Gregersen

doi:10.1016/j.ejmg.2021.104280

Phenotypic heterogeneity and mosaicism in Xia-Gibbs syndrome: Five Danish patients with novel variants in AHDC1

Soren L. Faergeman^*, Anders B. Bojesen, Maria Rasmussen, Naja Becher, Lotte Andreasen, Brian N. Andersen, Emilie Erbs, Dorte L. Lildballe, Jens Erik K. Nielsen, Monica Zilmer, Trine Bjørg Hammer, Mikkel Andersen, Charlotte Brasch-Andersen, Christina R. Fagerberg, Niels O. Illum, Mette B. Thorup, Pernille A. Gregersen

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

5 Citations (Scopus)

Abstract

Xia-Gibbs syndrome (XGS) is a neurodevelopmental disorder characterized by intellectual disability, developmental delay, seizures, hypotonia, obstructive sleep apnoea and mild facial dysmorphism. Heterozygosity for loss-of-function variants in AHDC1, encoding the AT-hook DNA binding motif containing protein 1, were discovered in 2014 as the likely genetic cause of Xia-Gibbs syndrome. We present five patients with Xia-Gibbs syndrome caused by previously unreported variants in AHDC1. Two of the patients share a frameshift variant: c.2849del (p.(Pro950Argfs*192)) in AHDC1. Despite sharing this variant, the two patients show remarkable phenotypic differences underscoring the clinical heterogeneity of Xia-Gibbs syndrome. In addition, we present a case of Xia-Gibbs syndrome caused by mosaicism for an AHDC1 variant.

Original language	English
Article number	104280
Journal	European Journal of Medical Genetics
Volume	64
Issue	9
Number of pages	6
ISSN	1769-7212
DOIs	https://doi.org/10.1016/j.ejmg.2021.104280
Publication status	Published - Sept 2021

Keywords

AHDC1
Dysmorphism
Reverse phenotyping
Whole exome sequencing
Xia-gibbs syndrome

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10.1016/j.ejmg.2021.104280

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Faergeman, S. L., Bojesen, A. B., Rasmussen, M., Becher, N., Andreasen, L., Andersen, B. N., Erbs, E., Lildballe, D. L., Nielsen, J. E. K., Zilmer, M., Hammer, T. B., Andersen, M., Brasch-Andersen, C., Fagerberg, C. R., Illum, N. O., Thorup, M. B., & Gregersen, P. A. (2021). Phenotypic heterogeneity and mosaicism in Xia-Gibbs syndrome: Five Danish patients with novel variants in AHDC1. European Journal of Medical Genetics, 64(9), Article 104280. https://doi.org/10.1016/j.ejmg.2021.104280

@article{13a270cc37184690a558995275d1ab84,

title = "Phenotypic heterogeneity and mosaicism in Xia-Gibbs syndrome: Five Danish patients with novel variants in AHDC1",

abstract = "Xia-Gibbs syndrome (XGS) is a neurodevelopmental disorder characterized by intellectual disability, developmental delay, seizures, hypotonia, obstructive sleep apnoea and mild facial dysmorphism. Heterozygosity for loss-of-function variants in AHDC1, encoding the AT-hook DNA binding motif containing protein 1, were discovered in 2014 as the likely genetic cause of Xia-Gibbs syndrome. We present five patients with Xia-Gibbs syndrome caused by previously unreported variants in AHDC1. Two of the patients share a frameshift variant: c.2849del (p.(Pro950Argfs*192)) in AHDC1. Despite sharing this variant, the two patients show remarkable phenotypic differences underscoring the clinical heterogeneity of Xia-Gibbs syndrome. In addition, we present a case of Xia-Gibbs syndrome caused by mosaicism for an AHDC1 variant.",

keywords = "AHDC1, Dysmorphism, Reverse phenotyping, Whole exome sequencing, Xia-gibbs syndrome",

author = "Faergeman, {Soren L.} and Bojesen, {Anders B.} and Maria Rasmussen and Naja Becher and Lotte Andreasen and Andersen, {Brian N.} and Emilie Erbs and Lildballe, {Dorte L.} and Nielsen, {Jens Erik K.} and Monica Zilmer and Hammer, {Trine Bj{\o}rg} and Mikkel Andersen and Charlotte Brasch-Andersen and Fagerberg, {Christina R.} and Illum, {Niels O.} and Thorup, {Mette B.} and Gregersen, {Pernille A.}",

note = "Funding Information: We would like to thank the families for their participation in this study. The research project has not received any funding. Publisher Copyright: {\textcopyright} 2021",

year = "2021",

month = sep,

doi = "10.1016/j.ejmg.2021.104280",

language = "English",

volume = "64",

journal = "European Journal of Medical Genetics",

issn = "1769-7212",

publisher = "Elsevier Masson",

number = "9",

}

Faergeman, SL, Bojesen, AB, Rasmussen, M, Becher, N, Andreasen, L , Andersen, BN, Erbs, E, Lildballe, DL, Nielsen, JEK, Zilmer, M, Hammer, TB, Andersen, M, Brasch-Andersen, C, Fagerberg, CR, Illum, NO, Thorup, MB & Gregersen, PA 2021, 'Phenotypic heterogeneity and mosaicism in Xia-Gibbs syndrome: Five Danish patients with novel variants in AHDC1', European Journal of Medical Genetics, vol. 64, no. 9, 104280. https://doi.org/10.1016/j.ejmg.2021.104280

Phenotypic heterogeneity and mosaicism in Xia-Gibbs syndrome: Five Danish patients with novel variants in AHDC1. / Faergeman, Soren L.; Bojesen, Anders B.; Rasmussen, Maria et al.
In: European Journal of Medical Genetics, Vol. 64, No. 9, 104280, 09.2021.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Phenotypic heterogeneity and mosaicism in Xia-Gibbs syndrome

T2 - Five Danish patients with novel variants in AHDC1

AU - Faergeman, Soren L.

AU - Bojesen, Anders B.

AU - Rasmussen, Maria

AU - Becher, Naja

AU - Andreasen, Lotte

AU - Andersen, Brian N.

AU - Erbs, Emilie

AU - Lildballe, Dorte L.

AU - Nielsen, Jens Erik K.

AU - Zilmer, Monica

AU - Hammer, Trine Bjørg

AU - Andersen, Mikkel

AU - Brasch-Andersen, Charlotte

AU - Fagerberg, Christina R.

AU - Illum, Niels O.

AU - Thorup, Mette B.

AU - Gregersen, Pernille A.

PY - 2021/9

Y1 - 2021/9

N2 - Xia-Gibbs syndrome (XGS) is a neurodevelopmental disorder characterized by intellectual disability, developmental delay, seizures, hypotonia, obstructive sleep apnoea and mild facial dysmorphism. Heterozygosity for loss-of-function variants in AHDC1, encoding the AT-hook DNA binding motif containing protein 1, were discovered in 2014 as the likely genetic cause of Xia-Gibbs syndrome. We present five patients with Xia-Gibbs syndrome caused by previously unreported variants in AHDC1. Two of the patients share a frameshift variant: c.2849del (p.(Pro950Argfs*192)) in AHDC1. Despite sharing this variant, the two patients show remarkable phenotypic differences underscoring the clinical heterogeneity of Xia-Gibbs syndrome. In addition, we present a case of Xia-Gibbs syndrome caused by mosaicism for an AHDC1 variant.

AB - Xia-Gibbs syndrome (XGS) is a neurodevelopmental disorder characterized by intellectual disability, developmental delay, seizures, hypotonia, obstructive sleep apnoea and mild facial dysmorphism. Heterozygosity for loss-of-function variants in AHDC1, encoding the AT-hook DNA binding motif containing protein 1, were discovered in 2014 as the likely genetic cause of Xia-Gibbs syndrome. We present five patients with Xia-Gibbs syndrome caused by previously unreported variants in AHDC1. Two of the patients share a frameshift variant: c.2849del (p.(Pro950Argfs*192)) in AHDC1. Despite sharing this variant, the two patients show remarkable phenotypic differences underscoring the clinical heterogeneity of Xia-Gibbs syndrome. In addition, we present a case of Xia-Gibbs syndrome caused by mosaicism for an AHDC1 variant.

KW - AHDC1

KW - Dysmorphism

KW - Reverse phenotyping

KW - Whole exome sequencing

KW - Xia-gibbs syndrome

UR - http://www.scopus.com/inward/record.url?scp=85109430816&partnerID=8YFLogxK

U2 - 10.1016/j.ejmg.2021.104280

DO - 10.1016/j.ejmg.2021.104280

M3 - Journal article

C2 - 34229113

AN - SCOPUS:85109430816

SN - 1769-7212

VL - 64

JO - European Journal of Medical Genetics

JF - European Journal of Medical Genetics

IS - 9

M1 - 104280

ER -

Phenotypic heterogeneity and mosaicism in Xia-Gibbs syndrome: Five Danish patients with novel variants in AHDC1

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Keywords

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