Leukoencephalopathy in Al‐Raqad syndrome: Expanding the clinical and neuroimaging features caused by a biallelic novel missense variant in DCPS

Abstract

Al‐Raqad syndrome (ARS) is a rare autosomal recessive congenital disorder, associated mainly with developmental delay, and intellectual disability. This syndrome is caused by mutations in DCPS, encoding scavenger mRNA decapping enzyme, which plays a role in the 3‐prime‐end mRNA decay pathway. Whole‐exome sequencing was performed on an offspring of a consanguineous family presenting with developmental delay, intellectual disability, growth retardation, mild craniofacial abnormalities, cerebral and cerebellar atrophy, and white matter diffuse hypomyelination pattern. A novel biallelic missense variant, c.918G>C p. (Glu306Asp), in the DCPS gene was identified which was confirmed by sanger sequencing and segregation analysis subsequently. Few cases of ARS have been described up to now, and this study represents a 7‐years‐old boy presenting with central and peripheral nervous system impaired myelination in addition to ocular and dental manifestation, therefore outstretch both neuroimaging and clinical findings of this ultra‐rare syndrome.

mRNA-decapping associated DcpS enzyme controls critical steps of neuronal development

“…Regulation of RNA metabolism has emerged as a critical modulator of neuronal development. We and others recently reported that the RNA stability associated DcpS scavenger decapping enzyme is essential for normal cognitive function (Ahmed I et al 2015; Ng CK et al 2015; Alesi V et al 2018; Masoudi M et al 2020). Here, we demonstrated a functional role for the scavenger decapping activity in determining neuronal development.…”

“…Mutations in DcpS can lead to varying motor and developmental delays, and cognitive defects (Ahmed I et al 2015) ranging from mild to more severe phenotypes that also include microcephaly, musculoskeletal and craniofacial abnormalities referred to as Al-Raqad syndrome (ARS) (Ng CK et al 2015; Alesi V et al 2018; Masoudi M et al 2020). This is an intellectual disability disorder identified in four families that harbor mutations in their DcpS gene that negatively impacts decapping activity.…”