Major facilitator superfamily domain-containing 2A (MFSD2A) is required for brain uptake of Docosahexaenoic acid and Lysophosphatidylcholine, both are essential for the normal neural development and function. Mutations in MFSD2A dysregulate the activity of this transporter in brain endothelial cells and can lead to microcephaly. In this study, we describe an 11-year-old male who is affected by autosomal recessive primary microcephaly 15. This patient also shows severe intellectual disability, recurrent respiratory and renal infections, low birth weight, and developmental delay. After doing clinical and neuroimaging evaluations, due to heterogeneity of neurogenetic disorders, no narrow clinical diagnosis was possible, therefore, we utilized targeted-exome sequencing to identify any causative genetic factors. This revealed a homozygous in-frame deletion (NM_001136493.1: c.241_243del; p.(Val81del)) in the MFSD2A gene as the most likely disease-susceptibility variant which was confirmed by Sanger sequencing. Neuroimaging revealed lateral ventricular asymmetry, corpus callosum hypoplasia, type B of cisterna magna, and widening of Sylvian fissures. All of these novel phenotypes are associated with autosomal recessive primary microcephaly-15 (MCPH15). According to the genotype-phenotype data, p.(Val81del) can be considered a likely pathogenic variant leading to non-lethal microcephaly. However, further cumulative data and molecular approaches are required to accurately identify genotype-phenotype correlations in MFSD2A.
Keywords: Autosomal recessive primary microcephaly 15; In-frame variant; Intellectual disability; MFSD2A; Whole-exome sequencing.
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