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 Ø 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 Ø Andersen, Charlotte Brasch-Andersen, Christina R Fagerberg, Niels O Illum, Mette B Thorup, Pernille A Gregersen

Afdeling for Genetik DIA

8 Citationer (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.

Originalsprog	Engelsk
Artikelnummer	104280
Tidsskrift	European Journal of Medical Genetics
Vol/bind	64
Udgave nummer	9
Sider (fra-til)	1-6
Antal sider	6
ISSN	1769-7212
DOI	https://doi.org/10.1016/j.ejmg.2021.104280
Status	Udgivet - sep. 2021

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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. Ø., 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), 1-6. Artikel 104280. https://doi.org/10.1016/j.ejmg.2021.104280

Faergeman, SL, Bojesen, AB, Rasmussen, M, Becher, N, Andreasen, L, Andersen, BN, Erbs, E, Lildballe, DL, Nielsen, JEK, Zilmer, M, Hammer, TB, Andersen, MØ, 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, bind 64, nr. 9, 104280, s. 1-6. https://doi.org/10.1016/j.ejmg.2021.104280

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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 = "Adolescent, Adult, Craniofacial Abnormalities/genetics, DNA-Binding Proteins/genetics, Developmental Disabilities/genetics, Female, Foot Deformities/genetics, Frameshift Mutation, Humans, Male, Muscle Hypotonia/genetics, Phenotype, Syndrome, Young Adult, Reverse phenotyping, Dysmorphism, Whole exome sequencing, Xia-gibbs syndrome, AHDC1",

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 Andersen, {Mikkel {\O}} and Charlotte Brasch-Andersen and Fagerberg, {Christina R} and Illum, {Niels O} and Thorup, {Mette B} and Gregersen, {Pernille A}",

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year = "2021",

month = sep,

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

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AU - Faergeman, Soren L

AU - Bojesen, Anders B

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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 Ø

AU - Brasch-Andersen, Charlotte

AU - Fagerberg, Christina R

AU - Illum, Niels O

AU - Thorup, Mette B

AU - Gregersen, Pernille A

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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.

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KW - Male

KW - Muscle Hypotonia/genetics

KW - Phenotype

KW - Syndrome

KW - Young Adult

KW - Reverse phenotyping

KW - Dysmorphism

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

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