Novel <i>L1CAM</i> splice site mutation in a young male with L1 syndrome

Rehnberg, Malin; Jonasson, Jon; Gunnarsson, Cecilia

doi:10.1002/ajmg.a.33803

Cited by 5 publications

(2 citation statements)

References 21 publications

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“…These features were all present in Patient 1. The c.3458-1G>A mutation in Patient 1 is novel but a splice site mutation at the same position (c.3458-1G>C) has been reported in a male with L1 syndrome [7].…”

Section: Discussionmentioning

confidence: 84%

Massively Parallel Sequencing of Patients with Intellectual Disability, Congenital Anomalies and/or Autism Spectrum Disorders with a Targeted Gene Panel

et al. 2014

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Developmental delay and/or intellectual disability (DD/ID) affects 1–3% of all children. At least half of these are thought to have a genetic etiology. Recent studies have shown that massively parallel sequencing (MPS) using a targeted gene panel is particularly suited for diagnostic testing for genetically heterogeneous conditions. We report on our experiences with using massively parallel sequencing of a targeted gene panel of 355 genes for investigating the genetic etiology of eight patients with a wide range of phenotypes including DD/ID, congenital anomalies and/or autism spectrum disorder. Targeted sequence enrichment was performed using the Agilent SureSelect Target Enrichment Kit and sequenced on the Illumina HiSeq2000 using paired-end reads. For all eight patients, 81–84% of the targeted regions achieved read depths of at least 20×, with average read depths overlapping targets ranging from 322× to 798×. Causative variants were successfully identified in two of the eight patients: a nonsense mutation in the ATRX gene and a canonical splice site mutation in the L1CAM gene. In a third patient, a canonical splice site variant in the USP9X gene could likely explain all or some of her clinical phenotypes. These results confirm the value of targeted MPS for investigating DD/ID in children for diagnostic purposes. However, targeted gene MPS was less likely to provide a genetic diagnosis for children whose phenotype includes autism.

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Section: Discussionmentioning

confidence: 84%

Massively Parallel Sequencing of Patients with Intellectual Disability, Congenital Anomalies and/or Autism Spectrum Disorders with a Targeted Gene Panel

et al. 2014

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“…Regretfully, the clinical parameters in utero were not collected. To date, about 56 splicing mutations in L1CAM gene have been reported in HGMD: several studies have described the prenatal features associated with splicing mutations (Isik et al, 2018; Okamoto et al, 2004; Rehnberg et al, 2011; Serikawa et al, 2014; Sun et al, 2019). Among them, intrauterine hydrocephalus is the basic characteristic, it occurs at different gestations from 17 weeks to 36 weeks.…”

Section: Discussionmentioning

confidence: 99%

A novel splicing variation in L1CAM is responsible for recurrent fetal hydrocephalus

He,

Yao,

et al. 2023

Molec Gen & Gen Med

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BackgroundThe L1 cell adhesion molecule (L1CAM, OMIM 308840) gene is primarily expressed in the nervous system and encodes the L1 adhesion molecule protein. Variations in L1CAM cause a wide spectrum of X‐linked neurological disorders summarized as the L1 syndrome.MethodsWe report a 29‐year‐old pregnant woman who experienced multiple adverse pregnancy outcomes due to recurrent fetal hydrocephalus with an X‐linked recessive inheritance. Genomic DNA was extracted from the third aborted male fetus and analyzed via trio whole‐exome sequencing (WES). Total RNA was isolated from the pregnant woman to assess splicing variation at the mRNA level, and amniotic fluid was extracted from the woman for prenatal diagnosis on her fourth fetus.ResultsAll four male fetuses were affected by severe hydrocephalus. We identified a maternally derived hemizygous splicing variation NM_000425.5:[c.3046 + 1G > A]; NP_000416.1 p.(Gly1016AspfsTer6) (chrX:153130275) in Intron 22 of the L1CAM. This variation disrupts the donor splice site and causes the retention of Intron 22, which results in frame shift and a premature termination codon at position 1021 with the ability to produce a truncated protein without the fifth fibronectin‐repeat III, transmembrane, and cytoplasmic domains or to induce the degradation of mRNAs by nonsense‐mediated mRNA decay. The same hemizygous variant was also detected in the amniocytes.ConclusionThis report enhances our knowledge of genetic and phenotypic characteristics of X‐linked fetal hydrocephalus, providing a new genetic basis for prenatal diagnosis and pre‐implantation prenatal diagnosis.

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The L1 Family of Cell Adhesion Molecules: A Sickening Number of Mutations and Protein Functions

Hortsch

Nagaraj

Mualla

2013

Advances in Neurobiology

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Novel L1CAM splice site mutation in a young male with L1 syndrome

Cited by 5 publications

References 21 publications

Massively Parallel Sequencing of Patients with Intellectual Disability, Congenital Anomalies and/or Autism Spectrum Disorders with a Targeted Gene Panel

Massively Parallel Sequencing of Patients with Intellectual Disability, Congenital Anomalies and/or Autism Spectrum Disorders with a Targeted Gene Panel

A novel splicing variation in L1CAM is responsible for recurrent fetal hydrocephalus

The L1 Family of Cell Adhesion Molecules: A Sickening Number of Mutations and Protein Functions

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