Yamanaka Gaku, Goto Kanako, Hayashi Yukiko K, Miyajima Tasuku, Hoshika Akinori, Arahata Kiichi
Department of Pediatrics, Tokyo Medical University, Tokyo.
No To Hattatsu. 2002 Jul;34(4):318-24.
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant form of muscular dystrophy characterized by progressive weakness and wasting of the facial, shoulder-girdle and upper arm muscles. The gene locus for FSHD is mapped to the subtelomeric region of chromosome 4q35, in which smaller EcoRI fragments (10 to 33 kb) are detected in most families by Southern blot analysis. The purpose of this study is to clarify the frequency and clinical/genetical features of early-onset FSHD in Japanese patients with 4q35-FSHD. In a series of 231 patients from 145 families with 4q35-FSHD, there were 31 patients (13.4%; male: female = 12:19) of 29 families (20%) with early-onset FSHD, 16 of whom were sporadic. Genetic analysis revealed that they had significantly smaller sized EcoRI fragments (range, 10 to 23 kb; mean 14.1 kb) than the other patients (range, 12 to 33 kb; mean 19.6 kb) (p < 0.001, U-test). All patients with the smallest EcoRI fragments (10 to 11 kb) were sporadic cases with early onset. Mental retardation (10/11) and epilepsy (4/11) was often observed in them, but not in the other patients. In early-onset FSHD, tongue muscle involvement (8/31) and swallowing disturbance (2/31), which has been regarded as exclusion criteria of FSHD, were also present. The onset of gait disturbance was significantly earlier (mean age = 11.9) in early-onset FSHD compared to the other group (mean age = 28.7). All patients with early-onset FSHD showed gait disturbance before 28 years of age. In conclusion, Japanese early-onset FSHD patients tend to have large gene deletions on chromosome 4q35, and show severe and variable phenotypes.
面肩肱型肌营养不良症（FSHD）是一种常染色体显性遗传的肌营养不良症，其特征为面部、肩胛带和上臂肌肉进行性无力和萎缩。FSHD的基因座定位于4号染色体q35的亚端粒区域，在大多数家族中，通过Southern印迹分析可检测到较小的EcoRI片段（10至33kb）。本研究的目的是阐明日本4q35 - FSHD患者中早发型FSHD的发生率以及临床/遗传特征。在来自145个家族的231例4q35 - FSHD患者系列中，有29个家族（20%）的31例患者（13.4%；男∶女 = 12∶19）患有早发型FSHD，其中16例为散发病例。遗传分析显示，他们的EcoRI片段大小（范围为10至23kb；平均14.1kb）明显小于其他患者（范围为12至33kb；平均19.6kb）（p < 0.001，U检验）。所有EcoRI片段最小（10至11kb）的患者均为早发散发病例。他们中经常观察到智力发育迟缓（10/11）和癫痫（4/11），而其他患者中则未观察到。在早发型FSHD中，还存在舌肌受累（8/31）和吞咽障碍（2/31），而这一直被视为FSHD的排除标准。与其他组（平均年龄 = 28.7岁）相比，早发型FSHD患者步态障碍的发病明显更早（平均年龄 = 11.9岁）。所有早发型FSHD患者在28岁之前均出现步态障碍。总之，日本早发型FSHD患者倾向于在4号染色体q35上有大片段基因缺失，并表现出严重且多样的表型。
