Vargha-Khadem F, Watkins K E, Price C J, Ashburner J, Alcock K J, Connelly A, Frackowiak R S, Friston K J, Pembrey M E, Mishkin M, Gadian D G, Passingham R E
Cognitive Neuroscience Unit, Institute of Child Health, University College London Medical School, Wolfson Centre, Mecklenbourgh Square, London WC1N 2AP, United Kingdom.
Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12695-700. doi: 10.1073/pnas.95.21.12695.
Investigation of the three-generation KE family, half of whose members are affected by a pronounced verbal dyspraxia, has led to identification of their core deficit as one involving sequential articulation and orofacial praxis. A positron emission tomography activation study revealed functional abnormalities in both cortical and subcortical motor-related areas of the frontal lobe, while quantitative analyses of magnetic resonance imaging scans revealed structural abnormalities in several of these same areas, particularly the caudate nucleus, which was found to be abnormally small bilaterally. A recent linkage study [Fisher, S., Vargha-Khadem, F., Watkins, K. E., Monaco, A. P. & Pembry, M. E. (1998) Nat. Genet. 18, 168-170] localized the abnormal gene (SPCH1) to a 5. 6-centiMorgan interval in the chromosomal band 7q31. The genetic mutation or deletion in this region has resulted in the abnormal development of several brain areas that appear to be critical for both orofacial movements and sequential articulation, leading to marked disruption of speech and expressive language.
对一个三代KE家族进行的研究发现，该家族一半的成员患有明显的言语失用症，其核心缺陷被确定为涉及连续发音和口面部动作。一项正电子发射断层扫描激活研究显示，额叶的皮质和皮质下运动相关区域存在功能异常，而磁共振成像扫描的定量分析显示，这些相同区域中的几个区域存在结构异常，特别是尾状核，发现其双侧异常小。最近的一项连锁研究[费舍尔，S.，瓦尔加-哈德姆，F.，沃特金斯，K.E.，莫纳科，A.P.和彭布里，M.E.（1998年）《自然遗传学》18卷，第168 - 170页]将异常基因（SPCH1）定位到染色体带7q31的一个5.6厘摩区间。该区域的基因突变或缺失导致了几个脑区的异常发育，这些脑区似乎对口面部运动和连续发音都至关重要，从而导致言语和表达性语言的明显障碍。
