A Novel LAS1L Gene Mutation Associated with Impaired Growth and Developmental Delay and a Review with Previously...

Area of Science:

• Genetics
• Developmental Biology
• Molecular Biology

Background:

• Wilson-Turner syndrome (WTS) is an X-linked developmental disorder.
• It is associated with variants in the LAS1L gene, crucial for ribosome biogenesis.

Purpose of the Study:

• To report a case expanding the phenotypic spectrum of LAS1L-related disorders.
• To investigate a novel LAS1L variant in a patient with unexplained symptoms.

Main Methods:

• Exome sequencing to identify genetic variants.
• Functional analysis in HEK-293T cells to assess protein expression.
• Structural modeling to predict protein alterations.

Main Results:

• A novel hemizygous LAS1L frameshift variant (c.2082dup) was identified in a boy with growth retardation, developmental delay, and scoliosis.
• Functional studies indicated reduced LAS1L protein expression and partial loss of function.
• The patient's phenotype differed from classical WTS features.

Conclusions:

• This case broadens the understanding of LAS1L-related disorders.
• LAS1L variants should be considered in pediatric cases of unexplained growth failure, scoliosis, or developmental delay, even without typical WTS features.