Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tuebingen, Germany.
Am J Med Genet A. 2013 Apr;161A(4):860-4. doi: 10.1002/ajmg.a.35778. Epub 2013 Mar 12.
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.
ACSL4（FACL4，OMIM 300157）的突变或缺失是一种罕见的非综合征性 X 连锁智力障碍的原因。我们报告了一名 10 岁男性患者，其具有中度智力障碍、感觉神经性听力损失、面型异常、幽门狭窄和肠梗阻，通过 SNP 阵列分析发现存在 Xq22.3-q23 的新生缺失。缺失的 1.56 Mb 间隔包含 ACSL4 和八个相邻基因（GUCY2F、NXT2、KCNE1L、TMEM164、MIR3978、AMMECR1、SNORD96B 和 RGAG1）。与先前报道的在 AMME 复合物区域（Alport 综合征、智力障碍、中面部发育不良和椭圆形红细胞增多症，OMIM 300194）染色体异常的患者不同，该缺失不包含 Alport 综合征基因 COL4A5，这表明该区间的一个或多个其他基因的缺失是导致临床问题的原因。总之，本报告中的患者拓宽了我们对 Xq22.3-q23 染色体区域缺失的表型后果的认识，并进一步证明了 ACSL4 是 X 连锁智力障碍基因。
