Aicardi syndrome (AS) is a well-characterized neurodevelopmental disorder with an unknown etiology. In this study, we performed whole-exome sequencing in 11 female patients with the diagnosis of AS, in order to identify the disease-causing gene. In particular, we focused on detecting variants in the X chromosome, including the analysis of variants with a low number of sequencing reads, in case of somatic mosaicism. For 2 of the patients, we also sequenced the exome of the parents to search for de novo mutations. We did not identify any genetic variants likely to be damaging. Only one single missense variant was identified by the de novo analyses of the 2 trios, and this was considered benign. The failure to identify a disease gene in this study may be due to technical limitations of our study design, including the possibility that the genetic aberration leading to AS is situated in a non-exonic region or that the mutation is somatic and not detectable by our approach. Alternatively, it is possible that AS is genetically heterogeneous and that 11 patients are not sufficient to reveal the causative genes. Future studies of AS should consider designs where also non-exonic regions are explored and apply a sequencing depth so that also low-grade somatic mosaicism can be detected.

Exome sequencing fails to identify the genetic cause of aicardi syndrome / Lund, Caroline; Striano, Pasquale; Sorte, Hanne Sørmo; Parisi, Pasquale; Iacomino, Michele; Sheng, Ying; Vigeland, Magnus D; Øye, Anne Marte; Møller, Rikke Steensbjerre; Selmer, Kaja K; Zara, Federico. - In: MOLECULAR SYNDROMOLOGY. - ISSN 1661-8769. - 7:4(2016), pp. 234-238. [10.1159/000448367]

Exome sequencing fails to identify the genetic cause of aicardi syndrome

PARISI, Pasquale
Writing – Original Draft Preparation
;
2016

Abstract

Aicardi syndrome (AS) is a well-characterized neurodevelopmental disorder with an unknown etiology. In this study, we performed whole-exome sequencing in 11 female patients with the diagnosis of AS, in order to identify the disease-causing gene. In particular, we focused on detecting variants in the X chromosome, including the analysis of variants with a low number of sequencing reads, in case of somatic mosaicism. For 2 of the patients, we also sequenced the exome of the parents to search for de novo mutations. We did not identify any genetic variants likely to be damaging. Only one single missense variant was identified by the de novo analyses of the 2 trios, and this was considered benign. The failure to identify a disease gene in this study may be due to technical limitations of our study design, including the possibility that the genetic aberration leading to AS is situated in a non-exonic region or that the mutation is somatic and not detectable by our approach. Alternatively, it is possible that AS is genetically heterogeneous and that 11 patients are not sufficient to reveal the causative genes. Future studies of AS should consider designs where also non-exonic regions are explored and apply a sequencing depth so that also low-grade somatic mosaicism can be detected.
2016
agenesis of corpus callosum; aicardi syndrome; whole-exome sequencing; X chromosome
01 Pubblicazione su rivista::01a Articolo in rivista
Exome sequencing fails to identify the genetic cause of aicardi syndrome / Lund, Caroline; Striano, Pasquale; Sorte, Hanne Sørmo; Parisi, Pasquale; Iacomino, Michele; Sheng, Ying; Vigeland, Magnus D; Øye, Anne Marte; Møller, Rikke Steensbjerre; Selmer, Kaja K; Zara, Federico. - In: MOLECULAR SYNDROMOLOGY. - ISSN 1661-8769. - 7:4(2016), pp. 234-238. [10.1159/000448367]
File allegati a questo prodotto
File Dimensione Formato  
Lund_Exome-sequencing-fails_2016.pdf

solo gestori archivio

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 391.23 kB
Formato Adobe PDF
391.23 kB Adobe PDF   Contatta l'autore

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/904558
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 15
  • ???jsp.display-item.citation.isi??? 13
social impact