van der Vleuten A J, van Ravenswaaij-Arts C M, Frijns C J, Smits A P, Hageman G, Padberg G W, Kremer H
Department of Neurology, University Hospital, Nijmegen, The Netherlands.
Eur J Hum Genet. 1998 Jul-Aug;6(4):376-82. doi: 10.1038/sj.ejhg.5200229.
Spinal muscular atrophies are a heterogeneous group of disorders. They differ in time of onset, clinical presentation, progression, severity and mode of inheritance. In 1985 a Dutch family was described with a dominant, non-progressive spinal muscular atrophy presenting at birth with arthrogryposis (MIM 600175). Linkage analysis was performed in this family. After having excluded the loci for Werdnig-Hoffmann's disease and for dominant distal spinal muscular atrophy with upper limb predominance, we were able to localise the gene to a 10 cM interval between the markers D12S78 and D12S1646 on chromosome 12q23-q24. Recently, dominant scapuloperoneal spinal muscular atrophy has been localised to an overlapping interval. However, the clinical appearances of scapuloperoneal spinal muscular atrophy and the present disorder make allelism unlikely. In 1994, a second Dutch family with a disorder similar to the present one was described. We excluded linkage to markers of the 12q23-q24 region in this family and thereby proved genetic heterogeneity of this type of dominant, congenital and nonprogressive spinal muscular atrophy.
脊髓性肌萎缩症是一组异质性疾病。它们在发病时间、临床表现、进展、严重程度和遗传方式上存在差异。1985年，有一个荷兰家族被描述为患有显性、非进行性脊髓性肌萎缩症，出生时伴有关节挛缩（MIM 600175）。对这个家族进行了连锁分析。在排除了韦尔尼克-霍夫曼病和以肢体为主的显性远端脊髓性肌萎缩症的基因座后，我们能够将该基因定位到12号染色体q23-q24上标记D12S78和D12S1646之间10厘摩的区间内。最近，显性肩胛腓骨型脊髓性肌萎缩症已被定位到一个重叠区间。然而，肩胛腓骨型脊髓性肌萎缩症与当前疾病的临床表现使得它们不太可能是等位基因。1994年，又描述了另一个患有与当前疾病相似病症的荷兰家族。我们排除了这个家族与12q23-q24区域标记的连锁关系，从而证明了这种显性、先天性和非进行性脊髓性肌萎缩症的遗传异质性。
