Voit T, Kutz P, Leube B, Neuen-Jacob E, Schröder J M, Cavallotti D, Vaccario M L, Schaper J, Broich P, Cohn R, Baethmann M, Göhlich-Ratmann G, Scoppetta C, Herrmann R
Department of Pediatrics and Pediatric Neurology, University of Essen, Essen, Germany.
Neuromuscul Disord. 2001 Jan;11(1):11-9. doi: 10.1016/s0960-8966(00)00158-9.
In 1995 Laing et al. (Am J Hum Genet 56(1995)422) described a single family with nine members affected by an autosomal dominant infantile onset distal myopathy. This family generated a LOD score of 2.6 for a locus on chromosome 14. We describe two families with an infantile onset distal myopathy: a new family with four affected members and the family previously described by Scoppetta et al. (Acta Neurol Scand 92(1955)122) in both of which haplotype segregation was compatible with linkage to the same chromosome 14 locus, generating LOD scores of 0.9 at a penetrance of 100% for the markers D14S283 and D14S64 (theta=0) in both families. The loci for autosomal recessive hereditary inclusion body myopathy and Nonaka myopathy on chromosome 9 and for autosomal dominant distal myopathy of Markesberry-Griggs and Udd on chromosome 2q31-33 were excluded by linkage analysis. The disease followed a uniform course with selective wasting of the anterior tibial muscles, starting in infancy and recognizable by a characteristic clinical sign of the 'hanging big toe'. This was followed by slow progression, with involvement of the finger and wrist extensor muscles in the third decade and proximal limb muscles in the fourth decade. Interestingly, we also found evidence of an accompanying mild peripheral neuropathy in the oldest individual with hypomyelination of numerous large myelinated fibres. In addition, this patient's muscle biopsy also showed autophagic vacuoles and numerous intranuclear tubulo-filamentous inclusions of 15-20 nm diameter. Given that all three families with infantile onset distal myopathy are compatible with linkage to the same locus on chromosome 14, this study supports evidence for, and enlarges the clinical and neuropathological spectrum of the distal myopathy on chromosome 14.
1995年，莱恩等人（《美国人类遗传学杂志》56(1995)422）描述了一个有9名成员受常染色体显性遗传婴儿期起病的远端肌病影响的家族。该家族在14号染色体上的一个位点产生了2.6的对数优势分数（LOD score）。我们描述了两个婴儿期起病的远端肌病家族：一个有4名受累成员的新家族，以及斯科佩塔等人（《神经病学杂志》92(1955)122）之前描述的家族，在这两个家族中，单倍型分离与14号染色体上的同一位点连锁相符，在两个家族中，对于标记D14S283和D14S64，在100%的外显率下产生了0.9的LOD分数（θ=0）。通过连锁分析排除了9号染色体上常染色体隐性遗传包涵体肌病和野中肌病以及2q31 - 33染色体上马克斯贝里 - 格里格斯和乌德常染色体显性远端肌病的位点。该疾病病程一致，以胫前肌选择性萎缩为特征，始于婴儿期，其特征性临床体征为“下垂大脚趾”。随后病情缓慢进展，在第三个十年累及手指和腕伸肌，在第四个十年累及近端肢体肌肉。有趣的是，我们还在最年长个体中发现了伴有轻度周围神经病变的证据，有大量大的有髓纤维髓鞘形成不良。此外，该患者的肌肉活检还显示出自噬泡以及许多直径为15 - 20纳米的核内管状细丝包涵体。鉴于所有三个婴儿期起病的远端肌病家族都与14号染色体上的同一位点连锁相符，本研究支持了14号染色体远端肌病的证据，并扩大了其临床和神经病理学范围。
