PMID- 38255008
OWN - NLM
STAT- MEDLINE
DCOM- 20240124
LR  - 20240201
IS  - 2073-4425 (Electronic)
IS  - 2073-4425 (Linking)
VI  - 15
IP  - 1
DP  - 2024 Jan 18
TI  - Sodium Channel Gene Variants in Fetuses with Abnormal Sonographic Findings: 
      Expanding the Prenatal Phenotypic Spectrum of Sodium Channelopathies.
LID - 10.3390/genes15010119 [doi]
LID - 119
AB  - Voltage-gated sodium channels (VGSCs) are responsible for the initiation and 
      propagation of action potentials in the brain and muscle. Pathogenic variants in 
      genes encoding VGSCs have been associated with severe disorders including 
      epileptic encephalopathies and congenital myopathies. In this study, we 
      identified pathogenic variants in genes encoding the alpha subunit of VGSCs in the 
      fetuses of two unrelated families with the use of trio-based whole exome 
      sequencing, as part of a larger cohort study. Sanger sequencing was performed for 
      variant confirmation as well as parental phasing. The fetus of the first family 
      carried a known de novo heterozygous missense variant in the SCN2A gene 
      (NM_001040143.2:c.751G>A p.(Val251Ile)) and presented intrauterine growth 
      retardation, hand clenching and ventriculomegaly. Neonatally, the proband also 
      exhibited refractory epilepsy, spasms and MRI abnormalities. The fetus of the 
      second family was a compound heterozygote for two parentally inherited novel 
      missense variants in the SCN4A gene (NM_000334.4:c.4340T>C, p.(Phe1447Ser), 
      NM_000334.4:c.3798G>C, p.(Glu1266Asp)) and presented a severe prenatal phenotype 
      including talipes, fetal hypokinesia, hypoplastic lungs, polyhydramnios, ear 
      abnormalities and others. Both probands died soon after birth. In a subsequent 
      pregnancy of the latter family, the fetus was also a compound heterozygote for 
      the same parentally inherited variants. This pregnancy was terminated due to 
      multiple ultrasound abnormalities similar to the first pregnancy. Our results 
      suggest a potentially crucial role of the VGSC gene family in fetal development 
      and early lethality.
FAU - Hadjipanteli, Andrea
AU  - Hadjipanteli A
AUID- ORCID: 0009-0008-4401-7513
AD  - The Cyprus Institute of Neurology and Genetics, Cytogenetics and Genomics, 2371 
      Nicosia, Cyprus.
FAU - Theodosiou, Athina
AU  - Theodosiou A
AUID- ORCID: 0000-0003-4363-8162
AD  - The Cyprus Institute of Neurology and Genetics, Cytogenetics and Genomics, 2371 
      Nicosia, Cyprus.
FAU - Papaevripidou, Ioannis
AU  - Papaevripidou I
AD  - The Cyprus Institute of Neurology and Genetics, Cytogenetics and Genomics, 2371 
      Nicosia, Cyprus.
FAU - Evangelidou, Paola
AU  - Evangelidou P
AUID- ORCID: 0000-0001-5565-0666
AD  - The Cyprus Institute of Neurology and Genetics, Cytogenetics and Genomics, 2371 
      Nicosia, Cyprus.
FAU - Alexandrou, Angelos
AU  - Alexandrou A
AD  - The Cyprus Institute of Neurology and Genetics, Cytogenetics and Genomics, 2371 
      Nicosia, Cyprus.
FAU - Salameh, Nicole
AU  - Salameh N
AD  - The Cyprus Institute of Neurology and Genetics, Cytogenetics and Genomics, 2371 
      Nicosia, Cyprus.
FAU - Kallikas, Ioannis
AU  - Kallikas I
AD  - AAK Ultrasound and Fetal Medicine Centre, 2025 Nicosia, Cyprus.
FAU - Kakoullis, Kyriakos
AU  - Kakoullis K
AD  - Apollonion Private Hospital, 2054 Nicosia, Cyprus.
FAU - Frakala, Sofia
AU  - Frakala S
AD  - Ledra Clinic, 1060 Nicosia, Cyprus.
FAU - Oxinou, Christina
AU  - Oxinou C
AD  - Christina Oxinou Histopathology/Cytology Laboratory, 1065 Nicosia, Cyprus.
FAU - Marnerides, Andreas
AU  - Marnerides A
AD  - Guy's and St Thomas' NHS Foundation Trust, London SE1 7EH, UK.
FAU - Kousoulidou, Ludmila
AU  - Kousoulidou L
AUID- ORCID: 0000-0002-9774-262X
AD  - The Cyprus Institute of Neurology and Genetics, Cytogenetics and Genomics, 2371 
      Nicosia, Cyprus.
FAU - Anastasiadou, Violetta C
AU  - Anastasiadou VC
AD  - Archbishop Makarios III Hospital, 2012 Nicosia, Cyprus.
FAU - Sismani, Carolina
AU  - Sismani C
AUID- ORCID: 0000-0002-9296-8347
AD  - The Cyprus Institute of Neurology and Genetics, Cytogenetics and Genomics, 2371 
      Nicosia, Cyprus.
LA  - eng
PT  - Journal Article
DEP - 20240118
PL  - Switzerland
TA  - Genes (Basel)
JT  - Genes
JID - 101551097
RN  - 0 (Vitamins)
RN  - 0 (Sodium Channels)
RN  - 0 (SCN4A protein, human)
RN  - 0 (NAV1.4 Voltage-Gated Sodium Channel)
SB  - IM
MH  - Female
MH  - Pregnancy
MH  - Humans
MH  - *Channelopathies
MH  - Cohort Studies
MH  - Vitamins
MH  - Sodium Channels
MH  - Fetus/diagnostic imaging
MH  - *Abnormalities, Multiple
MH  - NAV1.4 Voltage-Gated Sodium Channel
PMC - PMC10815715
OTO - NOTNLM
OT  - SCN2A
OT  - SCN4A
OT  - epileptic encephalopathy
OT  - severe fetal congenital myopathy 22B
OT  - voltage-gated sodium channels
OT  - whole-exome sequencing
COIS- The authors declare no conflicts of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript; or in the decision to publish the results.
EDAT- 2024/01/23 06:43
MHDA- 2024/01/24 06:43
PMCR- 2024/01/18
CRDT- 2024/01/23 01:05
PHST- 2023/12/21 00:00 [received]
PHST- 2024/01/08 00:00 [revised]
PHST- 2024/01/17 00:00 [accepted]
PHST- 2024/01/24 06:43 [medline]
PHST- 2024/01/23 06:43 [pubmed]
PHST- 2024/01/23 01:05 [entrez]
PHST- 2024/01/18 00:00 [pmc-release]
AID - genes15010119 [pii]
AID - genes-15-00119 [pii]
AID - 10.3390/genes15010119 [doi]
PST - epublish
SO  - Genes (Basel). 2024 Jan 18;15(1):119. doi: 10.3390/genes15010119.