PMID- 38125503
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231222
IS  - 2405-8440 (Print)
IS  - 2405-8440 (Electronic)
IS  - 2405-8440 (Linking)
VI  - 9
IP  - 12
DP  - 2023 Dec
TI  - CHD2 pathogenic nonsense variant in a three-generation family with variable 
      phenotype and a paracentric inversion 16: Case report.
PG  - e22987
LID - 10.1016/j.heliyon.2023.e22987 [doi]
LID - e22987
AB  - Chromosomal inversions are usually balanced structural chromosomal rearrangements 
      that do not have an impact on the clinical phenotype of a carrier. The main 
      clinical consequence of inversions is the risk for unbalanced gametes and 
      offspring with severe phenotypes. Rarely though, inversions are associated with a 
      phenotype, mainly due to submicroscopic Copy Number Variants (CNVs) or disruption 
      at the breakpoints of a functionally important gene and/or genomic elements. In 
      this study, a paracentric inversion of chromosome 16 [inv(16)(q22.3q24.1)] was 
      identified in a three-generation family with discordant phenotypes with/without 
      epilepsy and/or intellectual impairment, as well as with an unaffected carrier. 
      This finding was confirmed by fluorescence in situ hybridization (FISH). Genetic 
      investigation, initially with chromosomal microarray (CMA), did not reveal any 
      copy number variants. Finally, Clinical Exome Sequencing (CES), detected the 
      presence of a pathogenic nonsense variant (rs797044912) in the Chromodomain 
      Helicase DNA-binding protein 2 (CHD2) gene [NM_001271.4:c.5035C>T 
      p.(Arg1679Ter)]. CHD2 pathogenic variants have been associated with Developmental 
      and Epileptic Encephalopathy-94 (DEE-94), a rare yet severe condition, 
      characterized by developmental delay, seizures with an early onset, intellectual 
      impairment, autism spectrum disorder, and sometimes behavioral issues. Family 
      testing showed that the variant segregated with phenotypic heterogeneity in the 
      affected individuals and appears to be causative. To the best of our knowledge, 
      this is the first CHD2 pathogenic variant segregating in a three-generation 
      family and the fourth familial case reported. These results further support our 
      previous findings that familial, balanced rearrangements with discordant 
      phenotypes in the same family are, in the vast majority, coincidental.
CI  - (c) 2023 The Authors.
FAU - Angelopoulou, Eleni
AU  - Angelopoulou E
AD  - Laboratory of Medical Genetics, University General Hospital of Patras, 26504 Rio, 
      Greece.
FAU - Theodosiou, Athina
AU  - Theodosiou A
AD  - Department of Cytogenetics and Genomics, The Cyprus Institute of Neurology and 
      Genetics, 2371, Nicosia, Cyprus.
FAU - Papaevripidou, Ioannis
AU  - Papaevripidou I
AD  - Department of Cytogenetics and Genomics, The Cyprus Institute of Neurology and 
      Genetics, 2371, Nicosia, Cyprus.
FAU - Alexandrou, Angelos
AU  - Alexandrou A
AD  - Department of Cytogenetics and Genomics, The Cyprus Institute of Neurology and 
      Genetics, 2371, Nicosia, Cyprus.
FAU - Liehr, Thomas
AU  - Liehr T
AD  - Jena University Hospital, Friedrich Schiller University, Institute of Human 
      Genetics, 07747 Jena, Germany.
FAU - Gyftodimou, Yolanda
AU  - Gyftodimou Y
AD  - ATG-ACCESS TO GENOME, Michalakopoulou 139, 11528 Athens, Greece.
FAU - Stefanou, Eunice G
AU  - Stefanou EG
AD  - Laboratory of Medical Genetics, University General Hospital of Patras, 26504 Rio, 
      Greece.
FAU - Sismani, Carolina
AU  - Sismani C
AD  - Department of Cytogenetics and Genomics, The Cyprus Institute of Neurology and 
      Genetics, 2371, Nicosia, Cyprus.
LA  - eng
PT  - Case Reports
DEP - 20231128
PL  - England
TA  - Heliyon
JT  - Heliyon
JID - 101672560
PMC - PMC10731059
OTO - NOTNLM
OT  - CHD2
OT  - Clinical exome sequencing (CES)
OT  - Developmental epileptic encephalopathy
OT  - Familial
OT  - Inherited
OT  - Paracentric inversion 16
OT  - Seizure
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2023/12/21 06:42
MHDA- 2023/12/21 06:43
PMCR- 2023/11/28
CRDT- 2023/12/21 04:13
PHST- 2023/01/23 00:00 [received]
PHST- 2023/06/27 00:00 [revised]
PHST- 2023/11/23 00:00 [accepted]
PHST- 2023/12/21 06:43 [medline]
PHST- 2023/12/21 06:42 [pubmed]
PHST- 2023/12/21 04:13 [entrez]
PHST- 2023/11/28 00:00 [pmc-release]
AID - S2405-8440(23)10195-2 [pii]
AID - e22987 [pii]
AID - 10.1016/j.heliyon.2023.e22987 [doi]
PST - epublish
SO  - Heliyon. 2023 Nov 28;9(12):e22987. doi: 10.1016/j.heliyon.2023.e22987. 
      eCollection 2023 Dec.