Deguchi Kimiko, Clewing Johanna M, Elizondo Leah I, Hirano Ryuki, Huang Cheng, Choi Kunho, Sloan Emily A, Lücke Thomas, Marwedel Katja M, Powell Ralph D, Santa Cruz Karen, Willaime-Morawek Sandrine, Inoue Ken, Lou Shu, Northrop Jennifer L, Kanemura Yonehiro, van der Kooy Derek, Okano Hideyuki, Armstrong Dawna L, Boerkoel Cornelius F
Department of Pathology, Baylor College of Medicine, Houston, Texas, USA.
J Neuropathol Exp Neurol. 2008 Jun;67(6):565-77. doi: 10.1097/NEN.0b013e3181772777.
Schimke immuno-osseous dysplasia (OMIM 242900) is an uncommon autosomal-recessive multisystem disease caused by mutations in SMARCAL1 (swi/snf-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), a gene encoding a putative chromatin remodeling protein. Neurologic manifestations identified to date relate to enhanced atherosclerosis and cerebrovascular disease. Based on a clinical survey, we determined that half of Schimke immuno-osseous dysplasia patients have a small head circumference, and 15% have social, language, motor, or cognitive abnormalities. Postmortem examination of 2 Schimke immuno-osseous dysplasia patients showed low brain weights and subtle brain histologic abnormalities suggestive of perturbed neuron-glial migration such as heterotopia, irregular cortical thickness, incomplete gyral formation, and poor definition of cortical layers. We found that SMARCAL1 is highly expressed in the developing and adult mouse and human brain, including neural precursors and neuronal lineage cells. These observations suggest that SMARCAL1 deficiency may influence brain development and function in addition to its previously recognized effect on cerebral circulation.
施姆克免疫性骨发育不良（OMIM 242900）是一种罕见的常染色体隐性多系统疾病，由SMARCAL1（与swi/snf相关、基质相关、肌动蛋白依赖性染色质调节因子，a类亚家族样1）基因突变引起，该基因编码一种假定的染色质重塑蛋白。迄今为止确定的神经系统表现与动脉粥样硬化和脑血管疾病的加重有关。基于一项临床调查，我们确定一半的施姆克免疫性骨发育不良患者头围较小，15%的患者存在社交、语言、运动或认知异常。对2例施姆克免疫性骨发育不良患者的尸检显示脑重量较低，脑组织学存在细微异常，提示神经元-胶质细胞迁移受到干扰，如异位、皮质厚度不规则、脑回形成不完全以及皮质层界限不清。我们发现SMARCAL1在发育中的和成年小鼠及人类大脑中高度表达，包括神经前体细胞和神经元谱系细胞。这些观察结果表明，SMARCAL1缺乏可能除了对脑循环有先前已认识到的影响外，还会影响大脑发育和功能。
