Spastic tetraplegia, thin corpus callosum, and progressive microcephaly (SPATCCM) are linked to SLC1A4 genetic variants since the first reported case in 2015. SLC1A4 encodes for the neutral amino acid transporter ASCT1 which is involved in the transportation of serine between astrocytes and neurons. Although most of the reported cases are of Ashkenazi Jewish ancestry, SPATCCM has also been reported in Irish, Italian, Czech, Palestinian, and Pakistani ethnicities. Herein, we report two Pakistani male siblings from a non-consanguineous marriage presented with global developmental delay associated with spastic quadriplegia, microcephaly, and infantile spasm. Since infancy, both siblings suffered from microcephaly with brain MRI demonstrating generalized atrophy of the frontal, temporal, and parietal lobes with a prominence of the subarachnoid spaces, widening of the Sylvian fissures, and enlargement of the ventricular system not compatible with the chronological age of both patients associated with thinning of the corpus callosum. Whole-exome sequencing of both affected brothers revealed novel compound heterozygous variants in the SLC1A4 gene (NM_003038) segregating from their parents. The maternal c.971delA (p.N324Tfs*29) deletion variant disturbs the transcript reading frame leading to the generation of a premature stop codon and its subsequent degradation by nonsense-mediated mRNA decay as detected through expression analysis. The paternal c.542C > T (p.S181F) missense variant was predicted deleterious via multiple in silico prediction tools as the amino acid substitution is speculated to affect the overall ASCT1 structural confirmation due to the loss of an H-bond at the core of the protein at this position which might affect its function as concluded from the simulation analysis. The presented cases expand the genetic and clinical spectrum of ASCT1 deficiency and support the importance of including SLC1A4 gene screening in infants with unexplained global neurodevelopmental delay regardless of ethnicity.

Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE), characterized by chronic and progressive inflammation of the kidneys. As with many other autoimmune diseases, LN is a multifactorial disease caused by genetic and environmental factors. Globally, LN can affect around 60% of SLE patients, and it was observed to be less frequent and severe in Caucasian patients compared to other ethnic groups, including Arabs. Data on LN in the United Arab Emirates (UAE) are scattered and scarce in literature. Nevertheless, LN is common, occurring in around 43%–55% of SLE patients in the UAE. Anecdotally, the demographics and clinical features of SLE in the UAE have been distinct. However, the paucity of supporting literature makes it difficult to draw meaningful conclusions. Over the past two decades, there have been improvements in understanding the pathogenesis of LN; however, many cellular and molecular mechanisms which are implicated in the disease development and progression remain ambiguous. Investigating the clinical, pathological, and genetic characteristics of LN in different cohorts of patients is of importance for a better understanding of its pathogenesis, and thus improving its outcome. As a result, we acknowledge the need for large-scale epidemiological, clinical, and genetic investigation of LN cohorts in the UAE and surrounding regions.