Novel Familial IQSEC2 Pathogenic Sequence Variant Associated
With Neurodevelopmental Disorders and Epilepsy

J 2020

Novel Familial IQSEC2 Pathogenic Sequence Variant Associated With Neurodevelopmental Disorders and Epilepsy

WAYHELOVÁ, Markéta, Michal RYZÍ, Jan OPPELT, Eva HLADÍLKOVÁ, Vladimíra VALLOVÁ et. al.

Basic information

Original name

Novel Familial IQSEC2 Pathogenic Sequence Variant Associated With Neurodevelopmental Disorders and Epilepsy

Authors

WAYHELOVÁ, Markéta (203 Czech Republic, belonging to the institution), Michal RYZÍ (203 Czech Republic), Jan OPPELT (203 Czech Republic, belonging to the institution), Eva HLADÍLKOVÁ (203 Czech Republic), Vladimíra VALLOVÁ (703 Slovakia, belonging to the institution), Lenka KRSKOVÁ (203 Czech Republic), Marcela VILÉMOVÁ (203 Czech Republic), Hana POLÁČKOVÁ (203 Czech Republic, belonging to the institution), Renata GAILLYOVÁ (203 Czech Republic) and Petr KUGLÍK (203 Czech Republic, guarantor, belonging to the institution)

Edition

Neurogenetics, New York, Springer, 2020, 1364-6745

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10603 Genetics and heredity

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 2.660

RIV identification code

RIV/00216224:14310/20:00115870

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1007/s10048-020-00616-3

UT WoS

000541406100001

Keywords in English

neurodevelopmental disorders; epilepsy; targeted NGS; pathogenic sequence variant; IQSEC2 gene

Abstract

V originále

Pathogenic sequence variants in the IQ motif– and Sec7 domain–containing protein 2 (IQSEC2) gene have been confirmed as causative in the aetiopathogenesis of neurodevelopmental disorders (intellectual disability, autism) and epilepsy. We report on a case of a family with three sons; two of them manifest delayed psychomotor development and epilepsy. Initially proband A was examined using a multistep molecular diagnostics algorithm, including karyotype and array-comparative genomic hybridization analysis, both with negative results. Therefore, probands A and B and their unaffected parents were enrolled for an analysis using targeted “next-generation” sequencing (NGS) with a gene panel ClearSeq Inherited DiseaseXT (Agilent Technologies) and verification analysis by Sanger sequencing. A novel frameshift variant in the X-linked IQSEC2 gene NM_001111125.2:c.1813_1814del, p.(Asp605Profs*3) on protein level, was identified in both affected probands and their asymptomatic mother, having skewed X chromosome inactivation (XCI) (100:0). As the IQSEC2 gene is a known gene escaping from XCI in humans, we expect the existence of mechanisms maintaining the normal or enough level of the IQSEC2 protein in the asymptomatic mother. Further analyses may help to the characterization of the presented novel frameshift variant in the IQSEC2 gene as well as to elucidate the mechanisms leading to the rare asymptomatic phenotypes in females.

Links

MUNI/A/1127/2019, interní kód MU

Name: Podpora výzkumné činnosti studentů molekulární biologie a genetiky 8 (Acronym: MBG 8)

Investor: Masaryk University, Category A

NU20-07-00145, research and development project

Name: Úloha patogenních genetických variant detekovaných pomocí exomového sekvenování v etiologii dětských neurovývojových onemocnění

Investor: Ministry of Health of the CR, Subprogram 1 - standard

90132, large research infrastructures

Name: NCMG II

Citovat

WAYHELOVÁ, Markéta, Michal RYZÍ, Jan OPPELT, Eva HLADÍLKOVÁ, Vladimíra VALLOVÁ, Lenka KRSKOVÁ, Marcela VILÉMOVÁ, Hana POLÁČKOVÁ, Renata GAILLYOVÁ and Petr KUGLÍK. Novel Familial IQSEC2 Pathogenic Sequence Variant Associated With Neurodevelopmental Disorders and Epilepsy. Neurogenetics. New York: Springer, 2020, vol. 21, No 4, p. 269-278. ISSN 1364-6745. Available from: https://dx.doi.org/10.1007/s10048-020-00616-3.

@article{1668055,
   author = {Wayhelová, Markéta and Ryzí, Michal and Oppelt, Jan and Hladílková, Eva and Vallová, Vladimíra and Krsková, Lenka and Vilémová, Marcela and Poláčková, Hana and Gaillyová, Renata and Kuglík, Petr},
   article_location = {New York},
   article_number = {4},
   doi = {http://dx.doi.org/10.1007/s10048-020-00616-3},
   keywords = {neurodevelopmental disorders; epilepsy; targeted NGS; pathogenic sequence variant; IQSEC2 gene},
   language = {eng},
   issn = {1364-6745},
   journal = {Neurogenetics},
   title = {Novel Familial IQSEC2 Pathogenic Sequence Variant Associated With Neurodevelopmental Disorders and Epilepsy},
   url = {https://link.springer.com/article/10.1007/s10048-020-00616-3},
   volume = {21},
   year = {2020}
}

TY  - JOUR
ID  - 1668055
AU  - Wayhelová, Markéta - Ryzí, Michal - Oppelt, Jan - Hladílková, Eva - Vallová, Vladimíra - Krsková, Lenka - Vilémová, Marcela - Poláčková, Hana - Gaillyová, Renata - Kuglík, Petr
PY  - 2020
TI  - Novel Familial IQSEC2 Pathogenic Sequence Variant Associated With Neurodevelopmental Disorders and Epilepsy
JF  - Neurogenetics
VL  - 21
IS  - 4
SP  - 269-278
EP  - 269-278
PB  - Springer
SN  - 13646745
KW  - neurodevelopmental disorders
KW  - epilepsy
KW  - targeted NGS
KW  - pathogenic sequence variant
KW  - IQSEC2 gene
UR  - https://link.springer.com/article/10.1007/s10048-020-00616-3
L2  - https://link.springer.com/article/10.1007/s10048-020-00616-3
N2  - Pathogenic sequence variants in the IQ motif– and Sec7 domain–containing protein 2 (IQSEC2) gene have been confirmed as causative in the aetiopathogenesis of neurodevelopmental disorders (intellectual disability, autism) and epilepsy. We report on a case of a family with three sons; two of them manifest delayed psychomotor development and epilepsy. Initially proband A was examined using a multistep molecular diagnostics algorithm, including karyotype and array-comparative genomic hybridization analysis, both with negative results. Therefore, probands A and B and their unaffected parents were enrolled for an analysis using targeted “next-generation” sequencing (NGS) with a gene panel ClearSeq Inherited DiseaseXT (Agilent Technologies) and verification analysis by Sanger sequencing. A novel frameshift variant in the X-linked IQSEC2 gene NM_001111125.2:c.1813_1814del, p.(Asp605Profs*3) on protein level, was identified in both affected probands and their asymptomatic mother, having skewed X chromosome inactivation (XCI) (100:0). As the IQSEC2 gene is a known gene escaping from XCI in humans, we expect the existence of mechanisms maintaining the normal or enough level of the IQSEC2 protein in the asymptomatic mother. Further analyses may help to the characterization of the presented novel frameshift variant in the IQSEC2 gene as well as to elucidate the mechanisms leading to the rare asymptomatic phenotypes in females.
ER  -

WAYHELOVÁ, Markéta, Michal RYZÍ, Jan OPPELT, Eva HLADÍLKOVÁ, Vladimíra VALLOVÁ, Lenka KRSKOVÁ, Marcela VILÉMOVÁ, Hana POLÁČKOVÁ, Renata GAILLYOVÁ and Petr KUGLÍK. Novel Familial IQSEC2 Pathogenic Sequence Variant Associated With Neurodevelopmental Disorders and Epilepsy. \textit{Neurogenetics}. New York: Springer, 2020, vol.~21, No~4, p.~269-278. ISSN~1364-6745. Available from: https://dx.doi.org/10.1007/s10048-020-00616-3.

Detailed Information on Publication Record