Hayashi Shin, Okamoto Nobuhiko, Makita Yoshio, Hata Akira, Imoto Issei, Inazawa Johji
Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan.
Am J Med Genet A. 2008 Nov 15;146A(22):2905-10. doi: 10.1002/ajmg.a.32519.
Here we report on a 1-year-old Japanese girl with psychomotor retardation, bilateral congenital corneal opacity and bilateral postaxial polysyndactyly of the feet. Although she had a normal female karyotype, our in-house bacterial artificial chromosome (BAC)-based array-CGH analysis successfully detected at least a 2.7-Mb heterozygous deletion at 14q22.1-q22.3 harboring 18 protein-coding genes. Among the genes, BMP4 was a candidate for the gene causing the abnormalities of both the eye and digits. It was previously reported that the BMP family was correlated with the morphogenesis of digits and ocular development, and Bmp4 heterozygous null mice revealed skeletal abnormalities including polydactyly and ocular anterior segment abnormalities. Patients with a deletion including BMP4 also hadabnormalities of the eye and digits. These previous reports support that a haplo-insufficiency of the BMP4 gene likely caused the congenital ocular and digit abnormalities. Moreover, among the other genes contained in the deletion, GMFB is a candidate for the gene responsible for the psychomotor retardation.
我们在此报告一名1岁日本女孩，她有精神运动发育迟缓、双侧先天性角膜混浊和双侧足部轴后多指畸形。尽管她具有正常的女性核型，但我们基于细菌人工染色体（BAC）的内部阵列比较基因组杂交（array-CGH）分析成功检测到14q22.1-q22.3至少有一个2.7兆碱基的杂合缺失，该区域包含18个蛋白质编码基因。在这些基因中，骨形态发生蛋白4（BMP4）是导致眼睛和手指异常的候选基因。先前有报道称，BMP家族与手指形态发生和眼部发育相关，Bmp4杂合缺失小鼠表现出包括多指畸形在内的骨骼异常和眼前节异常。包含BMP4缺失的患者也有眼睛和手指异常。这些先前的报道支持BMP4基因的单倍体不足可能导致先天性眼部和手指异常。此外，在缺失区域包含的其他基因中，GMFB是导致精神运动发育迟缓的候选基因。
