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Case Report Open Access

A GABRB3 mutation (c.5G>A, p.Trp2*) in twins with generalized epilepsy with febrile seizures: A case report

  • Authors:
    • Shao-Min Lv
    • Kai-Xue Fan
    • Yan-E Wu
    • Jia-Hua Lv
    • Xiang-Yu Cui
    • Si-Jing Ren
    • Qiu-Bo Li
    • Jia Guo
    • Lin Wang
    • Rui-Han Liu
    • Qing-Xia Kong
  • View Affiliations / Copyright

    Affiliations: Clinical Medical College, Jining Medical University, Jining, Shandong 272000, P.R. China, Department of Pediatrics, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, P.R. China, Department of Neurology, Affiliated Jining Jinxiang Grand Hospital, Jining, Shandong 272200, P.R. China, The Second Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China, Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, P.R. China
    Copyright: © Lv et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 213
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    Published online on: September 4, 2025
       https://doi.org/10.3892/etm.2025.12963
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Abstract

In children aged 3 months to 6 years, convulsions that occur when the body temperature reaches >38˚C are referred to as febrile seizures (FS), provided that central nervous system infections and other metabolic etiologies are excluded. Generalized epilepsy with FS plus (GEFS+) refers to children who continue to suffer from FS after the age of 6 years with or without generalized and partial epileptic seizures. It is characterized by incomplete penetrance and genetic heterogeneity. In recent years, genetic techniques have undergone advancements, such that multiple genes can now be identified in clinical screenings, providing assistance in the diagnosis and delineation of diseases. Evidence suggests that mutations in a protein coding gene, γ‑aminobutyric acid type A receptor β3 subunit (GABRB3) may be associated with GEFS+. The present case reports female twins with febrile seizures that typically occurred after fever, with seizures still occurring after the age of 6. Their growth and development were uneventful, with their laboratory, imaging and electroencephalography results almost within normal limits. After inquiring their medical history, it was found that the father of the twins had similar seizures when he was young. Next, peripheral blood samples were collected from the twins and their parents for whole‑exome sequencing. The gene sequencing results showed that the twins and their father had a GABRB3 nonsense mutation (c.5G>A, p.Trp2*), which causes translation to terminate prematurely at the second tryptophan position. After consulting the literature, it was considered that they may have GABRB3 mutation‑associated GEFS+. After treatment with levetiracetam, the seizures in children have been effectively controlled and their growth and development have not been affected, which is within the normal range.
View Figures

Figure 1

Cranial MRI of the patient. (A) axial
view and (B) coronal view. The bilateral cerebral hemispheric
structure was symmetrical and the brain white matter contrast was
normal. However, patchy foci of slightly high T2-fluid-attenuated
inversion recovery abnormal signals were observed in the bilateral
occipital lobes (as indicated by the red circles).

Figure 2

Electroencephalography of the
patient. During the awake, quiet, and eye-closed state, bilateral
occipital regions exhibited 10.0-11.0 Hz alpha rhythm at 40-60 µV,
intermixed with sparse irregular waves. Activity was approximately
symmetrical on the left and right sides, indicating that the
regulation of amplitude modulation was acceptable. With the eyes
closed α inhibition and appearance was observed. Peak, spindle and
slow waves were observed during the sleep period, and the left and
right sides were generally symmetrical, indicating the absence of a
sleep cycle disorder. SENS, sensitivity; Fp1, frontopolar left;
Fp2, frontopolar right; F3, frontal left; F4, frontal right; C3,
central left; C4, central right; P3, parietal left; P4, parietal
right; O1, occipital left; O2, occipital right; F7, anterior
temporal left; F8, anterior temporal right; T3, mid-temporal left;
T4, mid-temporal right; T5, posterior temporal left; T6, posterior
temporal right; Fz, frontal midline; Cz, central midline; Pz,
parietal midline; -SAV, scalp average reference; -Aav, auricular
average reference; M, ground electrode.

Figure 3

Cranial MRI of the family of the
patient. Symmetrical bilateral cerebral hemispheric structures and
normal brain white matter contrasts were observed in (A) the
mother, (B) father and (C) elder twin sister of the patient,
without any abnormal signals.

Figure 4

Pedigree diagram of the four family
members. This diagram indicates that the father and twins were
affected, but the mother was not. Squares, male; circles, female;
shaded, individual was affected by the disease; non-shaded,
individual was not affected by the disease.

Figure 5

Sanger sequencing indicated that the
patient had a nonsense mutation in the GABRB3 gene. A
heterozygous nucleotide variation, c.5G>A, was identified in the
patient. The twin sister and father of the patient also had the
c.5G>A GABRB3 mutation. (A) patient with GABRB3
gene mutation. (B) Patient's father with GABRB3 gene
mutation. (C) Patient's mother with no variation found in
GABRB3. (D) Patient's sister with GABRB3 gene
mutation.
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Copy and paste a formatted citation
Spandidos Publications style
Lv S, Fan K, Wu Y, Lv J, Cui X, Ren S, Li Q, Guo J, Wang L, Liu R, Liu R, et al: A <em>GABRB3</em> mutation (c.5G&gt;A, p.Trp2*) in twins with generalized epilepsy with febrile seizures: A case report. Exp Ther Med 30: 213, 2025.
APA
Lv, S., Fan, K., Wu, Y., Lv, J., Cui, X., Ren, S. ... Kong, Q. (2025). A <em>GABRB3</em> mutation (c.5G&gt;A, p.Trp2*) in twins with generalized epilepsy with febrile seizures: A case report. Experimental and Therapeutic Medicine, 30, 213. https://doi.org/10.3892/etm.2025.12963
MLA
Lv, S., Fan, K., Wu, Y., Lv, J., Cui, X., Ren, S., Li, Q., Guo, J., Wang, L., Liu, R., Kong, Q."A <em>GABRB3</em> mutation (c.5G&gt;A, p.Trp2*) in twins with generalized epilepsy with febrile seizures: A case report". Experimental and Therapeutic Medicine 30.5 (2025): 213.
Chicago
Lv, S., Fan, K., Wu, Y., Lv, J., Cui, X., Ren, S., Li, Q., Guo, J., Wang, L., Liu, R., Kong, Q."A <em>GABRB3</em> mutation (c.5G&gt;A, p.Trp2*) in twins with generalized epilepsy with febrile seizures: A case report". Experimental and Therapeutic Medicine 30, no. 5 (2025): 213. https://doi.org/10.3892/etm.2025.12963
Copy and paste a formatted citation
x
Spandidos Publications style
Lv S, Fan K, Wu Y, Lv J, Cui X, Ren S, Li Q, Guo J, Wang L, Liu R, Liu R, et al: A <em>GABRB3</em> mutation (c.5G&gt;A, p.Trp2*) in twins with generalized epilepsy with febrile seizures: A case report. Exp Ther Med 30: 213, 2025.
APA
Lv, S., Fan, K., Wu, Y., Lv, J., Cui, X., Ren, S. ... Kong, Q. (2025). A <em>GABRB3</em> mutation (c.5G&gt;A, p.Trp2*) in twins with generalized epilepsy with febrile seizures: A case report. Experimental and Therapeutic Medicine, 30, 213. https://doi.org/10.3892/etm.2025.12963
MLA
Lv, S., Fan, K., Wu, Y., Lv, J., Cui, X., Ren, S., Li, Q., Guo, J., Wang, L., Liu, R., Kong, Q."A <em>GABRB3</em> mutation (c.5G&gt;A, p.Trp2*) in twins with generalized epilepsy with febrile seizures: A case report". Experimental and Therapeutic Medicine 30.5 (2025): 213.
Chicago
Lv, S., Fan, K., Wu, Y., Lv, J., Cui, X., Ren, S., Li, Q., Guo, J., Wang, L., Liu, R., Kong, Q."A <em>GABRB3</em> mutation (c.5G&gt;A, p.Trp2*) in twins with generalized epilepsy with febrile seizures: A case report". Experimental and Therapeutic Medicine 30, no. 5 (2025): 213. https://doi.org/10.3892/etm.2025.12963
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