Analysis of <scp>L1CAM</scp> gene mutation and imaging appearance in three Chinese families with <scp>L1</scp> syndrome: Three case reports

Gao, Shanshan; Zhao, Xuechao; Zhao, Ganye; Dai, Peng; Kong, Xiangdong

doi:10.1002/mgg3.2002

Cited by 5 publications

(2 citation statements)

References 24 publications

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“…In humans, mutations in L1 lead to the development of the L1 syndrome, which is characterized by intellectual disabilities, hydrocephalus of varying severity, spasticity and agenesis of the corpus callosum [41,42,67,68,[83][84][85]. In addition, one case was described in which the whole L1 gene was deleted in a child with L1 syndrome [86].…”

Section: Discussionmentioning

confidence: 99%

Mice Mutated in the First Fibronectin Domain of Adhesion Molecule L1 Show Brain Malformations and Behavioral Abnormalities

Granato,

Congiu,

Jakovcevski

et al. 2024

Biomolecules

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The X-chromosome-linked cell adhesion molecule L1 (L1CAM), a glycoprotein mainly expressed by neurons in the central and peripheral nervous systems, has been implicated in many neural processes, including neuronal migration and survival, neuritogenesis, synapse formation, synaptic plasticity and regeneration. L1 consists of extracellular, transmembrane and cytoplasmic domains. Proteolytic cleavage of L1’s extracellular and transmembrane domains by different proteases generates several L1 fragments with different functions. We found that myelin basic protein (MBP) cleaves L1’s extracellular domain, leading to enhanced neuritogenesis and neuronal survival in vitro. To investigate in vivo the importance of the MBP-generated 70 kDa fragment (L1-70), we generated mice with an arginine to alanine substitution at position 687 (L1/687), thereby disrupting L1’s MBP cleavage site and obliterating L1-70. Young adult L1/687 males showed normal anxiety and circadian rhythm activities but enhanced locomotion, while females showed altered social interactions. Older L1/687 males were impaired in motor coordination. Furthermore, L1/687 male and female mice had a larger hippocampus, with more neurons in the dentate gyrus and more proliferating cells in the subgranular layer, while the thickness of the corpus callosum and the size of lateral ventricles were normal. In summary, subtle mutant morphological changes result in subtle behavioral changes.

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Section: Discussionmentioning

confidence: 99%

Mice Mutated in the First Fibronectin Domain of Adhesion Molecule L1 Show Brain Malformations and Behavioral Abnormalities

Granato,

Congiu,

Jakovcevski

et al. 2024

Biomolecules

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“…Therefore, it is essential to undertake continuous ultrasound monitoring, genetic testing, brain MRIs, and TORCH infection evaluation for a comprehensive evaluation of fetal MV under the current guideline ( 2 , 17 ). Some studies have found that MV has recently been associated with monogenic disorders ( 18 , 19 ). For example, MV is found to be the most common prenatal ultrasound phenotype in MDS/PAFAH1B1-related lissencephaly ( 18 ).…”

Section: Discussionmentioning

confidence: 99%

A de novo heterozygous POU3F3 genotype for the p.(Q214*) variant in a fetus with transient isolated bilateral mild ventriculomegaly: a case report and review of the literature

Zhang,

Linpeng,

Teng

et al. 2023

Front. Pediatr.

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The prenatal prevalence of isolated ventriculomegaly is 0.039%–0.087%. Most isolated mild ventriculomegaly (MV) fetuses (>90%) have a favorable prognosis. However, 5.6% to 7.9% of fetuses with isolated MV have adverse neurodevelopmental outcomes. In this study, we reported the first case of prenatal Snijders Blok-Fisher syndrome (OMIM: #618604) caused by a truncating variant of POU3F3 (OMIM: *602480) in a fetus with transient isolated bilateral MV. The results of karyotype analysis, chromosomal microarray analysis, and TORCH infection evaluation for the fetus were all negative. However, a de novo likely pathogenic nonsense variant of NM_006236.3 (POU3F3): c.640C > T [rs1254251078] p.(Q214*) was identified by whole-exome sequencing (WES). Despite sufficient genetic counseling, the mother refused to undertake further brain magnetic resonance imaging (MRI) and decided to keep the fetus. She gave birth to a male infant through a full-term vaginal delivery. With a long-term follow-up, the infant unfortunately gradually presented with delayed motor development. The postnatal brain MRI of the proband showed dysplasia of the corpus callosum and ventriculomegaly. Considering the high probability of misdiagnosis for such cases, we further summarized the prenatal phenotypes from 19 reported patients with variants in POU3F3. The results revealed that 14 patients displayed a normal prenatal ultrasonographic manifestation, while only approximately 26.32% of fetuses showed MV or cysts without structural deformity. Thus our findings expand the variant spectrum of POU3F3 and suggest the importance of undertaking WES and brain MRI when the fetus has isolated bilateral MV.

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Analysis of L1CAM gene mutation and imaging appearance in three Chinese families with L1 syndrome: Three case reports

Gao

Zhao

et al. 2022

Molec Gen & Gen Med

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Background:The molecular mutations of the L1CAM gene and the imaging appearances of four fetuses with L1 syndrome from three independent Chinese families with a history of hydrocephalus were reported in this study. Two of the three are novel L1CAM variants. Methods:Results of clinical and imaging examinations of three Chinese families were collected. Fetal samples were collected by puncture, genomic DNA was extracted, whole-exome sequencing was performed, and the L1CAM gene mutation sites were verified by PCR and Sanger sequencing. Results:In this case report, we described the imaging appearance and investigated the mutations of the L1CAM gene in three Chinese families with a history of L1 syndrome; these included two nonsense mutations (c.262C>T and c.261C>G) and one splice-site mutation (c.524-1G>A). Two of these three are novel L1CAM variants: c.262C>T and c.261C>G. The results of the sonographic images of the affected fetuses showed severe hydrocephalus. Bilateral lateral ventricles were dilated in the fetuses with c.262C>T and c.261C>G mutations. The left ventricle was about 14 mm wide and the right was about 14 mm in the fetus with c.262C>T mutation. The left ventricle was about 24.9 mm wide and the right was about 23.9 mm in the fetus with c.261C>G mutation. The ultrasound examination of the fetus with c.524-1G>A mutation showed that the third ventricle (7.5 mm wide) was raised, and the fourth ventricle was communicated with the cisterna magna. The parents requested termination of the above pregnancy. Conclusion:The current study emphasizes the importance of combining family history, prenatal ultrasonography, and L1CAM mutation testing positive for the diagnosis of the L1 syndrome.

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Analysis of L1CAM gene mutation and imaging appearance in three Chinese families with L1 syndrome: Three case reports

Cited by 5 publications

References 24 publications

Mice Mutated in the First Fibronectin Domain of Adhesion Molecule L1 Show Brain Malformations and Behavioral Abnormalities

Mice Mutated in the First Fibronectin Domain of Adhesion Molecule L1 Show Brain Malformations and Behavioral Abnormalities

A de novo heterozygous POU3F3 genotype for the p.(Q214*) variant in a fetus with transient isolated bilateral mild ventriculomegaly: a case report and review of the literature

Analysis of L1CAM gene mutation and imaging appearance in three Chinese families with L1 syndrome: Three case reports

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