DCX variants in two unrelated Chinese families with subcortical band heterotopia: Two case reports and review of literature

Gao, Chunlai; Liu, Ning; Ma, Jian; Zhao, Jianshe; Zhao, Bing; Song, Fengling; Dong, Rui; Li, Zilong; Lv, Yuqiang; Liu, Yi; Gai, Zhongtao

doi:10.1016/j.heliyon.2023.e22323

Cited by 1 publication

(2 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More than 150 different variants of the DCX gene were reported, with a prevalence of missense variants (64.7%), followed by small deletions (8.5%), gross deletions (7.8%), nonsense variants (7.2%), small insertions (4.6%), splicing variants (4.6%), gross insertions (1.3%), small indel (0.7%), and complex rearrangement (0.7%) [14]. Missense variants are typically inherited, clustered in the evolutionarily conserved domains (N-DC and C-DC) and tend to cause less severe phenotypes than nonsense variants, which are often found in sporadic cases [13].…”

Section: Discussionmentioning

confidence: 99%

“…Several genetic variations, including missense, nonsense, frameshift, and deletions, were documented in both familial and sporadic cases, either as inherited mutations or de novo mutations. Inherited mutations, often missense, tend to result in less severe phenotypes compared to nonsense mutations, which lead to protein truncations [13,14]. Numerous studies propose that skewed X inactivation or low-level mosaicism may also contribute to the heterogeneity of phenotypes within families, especially among asymptomatic carriers.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Phenotypic Variability in Novel Doublecortin Gene Variants Associated with Subcortical Band Heterotopia

Procopio,

Fortunato,

Gagliardi

et al. 2024

IJMS

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%