The Study of Clinical Phenotypes and Analysis of Mutations in L1 Syndrome

L1CAM protein plays a crucial role during early development and mutations in L1CAM cause L1 syndrome. L1 syndrome demonstrates a highly variable presentation within and between families. The clinical symptoms of L1 syndrome include mental retardation, hydrocephalus, spasticity, aphasia, and adducted thumb. Mutations in L1CAM gene were found to affect structurally essential key residues in extracellular region of L1 leading to changes in protein binding properties. In most cases, these mutations create unexpected phenotypes which need to be understood thoroughly.

The L1 syndrome patients were identified by various phenotypes like mental retardation, hydrocephalus, aphasia, spasticity, adducted thumb, etc., and the patients or mental retardation (MR) children who had more than three symptoms. This study aimed to screen mutations in multiple exons by Sanger sequencing.

The present study employed primers which are designed for specific exons of L1CAM gene to amplify and sequence the amplified product to detect the mutations in L1 syndrome patients by the Sanger sequencing. Chi-square test was used to determine the mutation detection rate with the number of L1 syndrome phenotypes and several in silico programs were used to investigate potential effects of the variants.

The nine different mutations in six patients. The mutation detection rate was high (83.33%) in patients with more than one L1 syndrome phenotype and in patients with more than one affected member in a family compared to patients with single phenotypes and negative family history (16.6%).

The mutation detection rate was related to the presence of typical L1 syndrome phenotypes and the family history. Screening of L1CAM gene mutations in the Indian population is much needed to analyze the mutations and understand the mechanism underlying L1 disease. The present study has identified some novel mutations which are implicated in alterations in various biological functions during development leading to pathogenesis of L1 syndrome.