Postnatal microcephaly and retinal involvement expand the phenotype of RPL10-related disorder

Area of Science:

• Genetics
• Neuroscience
• Ophthalmology

Background:

• RPL10 gene variants cause X-linked intellectual disability (ID) and autism spectrum disorder (ASD).
• Previous reports noted retinitis pigmentosa in one case and microcephaly in half of affected individuals.

Purpose of the Study:

• To identify the genetic cause of ID, ASD, and congenital anomalies in four male children from three families.
• To investigate a potential genotype-phenotype correlation for a novel RPL10 variant.

Main Methods:

• Whole exome sequencing was performed on four male probands and their mothers.
• The identified RPL10 variant was analyzed for its predicted effect on protein structure and function.
• Clinical features of the affected individuals were thoroughly documented.

Main Results:

• Four male children carried a novel hemizygous missense variant, p.(Arg32Leu), in the RPL10 gene, inherited from their mothers.
• All affected boys presented with intellectual disability, dysmorphic features, progressive postnatal microcephaly, and retinal degeneration.
• The p.(Arg32Leu) variant is predicted to disrupt the RPL10 protein's 28S rRNA binding region.

Conclusions:

• The novel RPL10 variant p.(Arg32Leu) is associated with a distinct phenotype including intellectual disability, postnatal microcephaly, and retinal degeneration.
• Retinopathy and postnatal microcephaly may serve as key clinical indicators for RPL10-related disorders.
• The findings suggest a specific genotype-phenotype correlation, particularly for the retinal defect associated with the p.(Arg32Leu) variant.