Phenotypic Variability in Novel Doublecortin Gene Variants Associated with Subcortical Band Heterotopia.
Int J Mol Sci
; 25(10)2024 May 18.
Article
en En
| MEDLINE
| ID: mdl-38791543
ABSTRACT
Doublecortin, encoded by the DCX gene, plays a crucial role in the neuronal migration process during brain development. Pathogenic variants of the DCX gene are the major causes of the "lissencephaly (LIS) spectrum", which comprehends a milder phenotype like Subcortical Band Heterotopia (SBH) in heterozygous female subjects. We performed targeted sequencing in three unrelated female cases with SBH. We identified three DCX-related variants a novel missense (c.601A>G p.Lys201Glu), a novel nonsense (c.210C>G p.Tyr70*), and a previously identified nonsense (c.907C>T p.Arg303*) variant. The novel c.601A>G p.Lys201Glu variant shows a mother-daughter transmission pattern across four generations. The proband exhibits focal epilepsy and achieved seizure freedom with a combination of oxcarbazepine and levetiracetam. All other affected members have no history of epileptic seizures. Brain MRIs of the affected members shows predominant fronto-central SBH with mixed pachygyria on the overlying cortex. The two nonsense variants were identified in two unrelated probands with SBH, severe drug-resistant epilepsy and intellectual disability. These novel DCX variants further expand the genotypic-phenotypic correlations of lissencephaly spectrum disorders. Our documented phenotypic descriptions of three unrelated families provide valuable insights and stimulate further discussions on DCX-SBH cases.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fenotipo
/
Lisencefalias Clásicas y Heterotopias Subcorticales en Banda
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Proteína Doblecortina
Límite:
Adolescent
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Adult
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Child
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Child, preschool
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Female
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Humans
Idioma:
En
Revista:
Int J Mol Sci
/
Int. j. mol. sci. (Online)
/
International journal of molecular sciences (Online)
Año:
2024
Tipo del documento:
Article
País de afiliación:
Italia