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.

大脑摄取二十二碳六烯酸和溶血磷脂酰胆碱需要主要的促进子超家族域2A（MFSD2A），这对于正常的神经发育和功能都是必不可少的。MFSD2A中的突变在脑内皮细胞中该转运蛋白的活性失调，可导致小头畸形。在这项研究中，我们描述了一个11岁的男性，该个体受到常染色体隐性原发性小头畸形15的影响。该患者还表现出严重的智力残疾，反复呼吸道和肾脏感染，低出生体重和发育迟缓。在进行临床和神经影像学评估后，由于神经遗传疾病的异质性，不可能进行狭窄的临床诊断，因此，我们利用靶向外显子组测序来鉴定任何致病性遗传因素。在;（P（Val81del）c.241_243del NM_001136493.1）。这揭示了纯合的框内缺失MFSD2A该基因是最可能的疾病易感性变异体，已通过Sanger测序证实。神经影像学检查发现侧脑室不对称，call体发育不全，巨大的水罐B型以及西尔维安裂缝扩大。所有这些新的表型都与常染色体隐性遗传性原发性小头畸形15（MCPH15）相关。根据基因型-表型数据，p。（Val81del）可能被认为是导致非致命性小头畸形的致病性变异。但是，需要进一步的累积数据和分子方法来准确识别MFSD2A中的基因型-表型相关性。