Xq22.3–q23 deletion including ACSL4 in a patient with intellectual disability

Abstract

Mutations or deletions of ACSL4 (FACL4, OMIM 300157) are a rare cause of non-syndromic X-linked intellectual disability. We report on a 10-year-old male patient with moderate intellectual disability, sensorineural hearing loss, facial dysmorphism, pyloric stenosis, and intestinal obstruction in whom a de novo Xq22.3-q23 deletion was detected by SNP array analysis. The deleted 1.56 Mb interval harbored ACSL4 and eight neighboring genes (GUCY2F, NXT2, KCNE1L, TMEM164, MIR3978, AMMECR1, SNORD96B, and RGAG1). In contrast to previously reported patients with chromosome aberrations in the region of the AMME complex (Alport syndrome, intellectual disability, midface hypoplasia, and elliptocytosis, OMIM 300194), this deletion did not contain the Alport syndrome gene COL4A5, suggesting that loss of one or several of the other genes in this interval is responsible for the clinical problems. In summary, the patient reported here broadens our knowledge of the phenotypic consequences of deletions of chromosome region Xq22.3-q23 and provides further proof for ACSL4 as an X-linked intellectual disability gene.

Long-Chain Acyl-CoA Synthetase 4A Regulates Smad Activity and Dorsoventral Patterning in the Zebrafish Embryo

“…Likewise, heterozygous female mice display compromised uterus development and fertility, and only very rarely transmit the disrupted allele to offspring (Cho, 2001). Finally, Drosophila mutants are recessive lethal (McQuilton et al, 2012) and hypomorphs display defects in segmentation (Zhang et al, 2011) and development of the CNS (Gazou et al, 2013; Liu et al, 2011; Meloni et al, 2002a; Meloni et al, 2009; Piccini et al, 1998; Zhang et al, 2009). However, the molecular underpinnings of these phenotypes have yet to be described.…”

Xq22.3q23 microdeletion harboring TMEM164 and AMMECR1 genes: Two case reports confirming a recognizable phenotype with short stature, midface hypoplasia, intellectual delay, and elliptocytosis

“…These new cases provide further evidence that AMMECR1 gene deletions give rise to specific clinical features and suggest that full gene deletion or pathogenic variants lead to the same phenotype. Likewise larger Xq22.3q23 deletions including AMMECR1 (Gazou et al, ; Jonsson et al, ) yield a very similar phenotype with the exception of Alport syndrome, due to the absence of the COL4A5 gene (Jonsson et al, ). Interestingly, Rodriguez et al () reported two males with a Xq22.3q23 deletion involving COL4A5 but not AMMECR1 .…”

“…In these cases, the gene ACSL4 is proposed to be the best candidate gene to explain the intellectual deficiency. Bioinformatics analyses predicted that ACSL4 could directly interact with AMMECR1 (Andreoletti et al, ; Basel‐Vanagaite et al, ; Bath et al, 2006; Gazou et al, ). This data may explain why patients with Xq22.3q23 deletions without AMMECR1 could present with most of the clinical features of AMMECR1 mutated patients.…”

“…The AMME syndrome defined as the combination of Alport syndrome, intellectual disability, midface hypoplasia, and elliptocytosis (AMME, MIM300194) is known to be a contiguous gene syndrome associated with microdeletions in the region Xq22.3q23 (Bath et al, ; Gazou et al, ; Jonsson et al, ; Robson, Lowry, & Leung, ; Rodriguez et al, ). These microdeletions involve up to eight OMIM genes and in particular the disease associated genes GUCY2F , KCNE1L , COL4A5 , ACSL4 , and AMMECR1.…”

Gene Expression Profile and Signaling Pathways in MCF-7 Breast Cancer Cells Mediated by Acyl-Coa Synthetase 4 Overexpression

“…Studies on the physiological functions of ACSL4 have revealed possible roles in polyunsaturated fatty acid metabolism in brain, in steroidogenesis, in eicosanoid metabolism related to apoptosis and embryogenesis [8][9][10][11][12][13][14]. ACSL4 expression has also been associated with non-physiological functions such as mental retardation disorder [15,16] and cancer [2,3,17,18]. ACSL4 was first associated with cancer due to its abnormal expression in colon and hepatocellular carcinoma.…”