Department of Women's and Children's Health, Uppsala University Children's Hospital, Uppsala, Sweden.
Acta Paediatr. 2012 Aug;101(8):877-87. doi: 10.1111/j.1651-2227.2012.02708.x. Epub 2012 May 24.
Distal arthrogryposis is characterized by congenital contractures predominantly in hands and feet. Mutations in sarcomeric protein genes are involved in several types of distal arthrogryposis. Our aim is to describe clinical and molecular genetic findings in individuals with distal arthrogryposis and evaluate the genotype-phenotype correlation.
We investigated 39 patients from 21 families. Clinical history, including neonatal findings, joint involvement and motor function, was documented. Clinical examination was performed including evaluation of muscle strength. Molecular genetic investigations were carried out in 19 index cases. Muscle biopsies from 17 patients were analysed.
A pathogenic mutation was found in six families with 19 affected family members with autosomal dominant inheritance and in one child with sporadic occurrence. In three families and in one child with sporadic form, the identified mutation was de novo. Muscle weakness was found in 17 patients. Ambulation was affected in four patients and hand function in 28. Fourteen patients reported pain related to muscle and joint affection.
The clinical findings were highly variable between families and also within families. Mutations in the same gene were found in different syndromes suggesting varying clinical penetrance and expression, and different gene mutations were found in the same clinical syndrome demonstrating genetic heterogeneity.
远端型关节挛缩症的特征是手和脚先天挛缩。在几种类型的远端型关节挛缩症中，肌节蛋白基因突变。我们的目的是描述远端型关节挛缩症患者的临床和分子遗传学发现，并评估基因型-表型相关性。
我们调查了 21 个家族的 39 名患者。记录了临床病史，包括新生儿发现、关节受累和运动功能。进行了临床检查，包括肌肉力量评估。对 19 名指数病例进行了分子遗传学研究。分析了 17 名患者的肌肉活检。
在 6 个具有常染色体显性遗传的家族中有 19 名受影响的家族成员，在一个散发病例中有一个致病性突变。在 3 个家族和 1 个散发病例中，鉴定出的突变是新生的。17 名患者出现肌肉无力。4 名患者活动受限，28 名患者手部功能受限。14 名患者报告肌肉和关节受累引起的疼痛。
家族之间和家族内的临床发现高度不同。相同基因的突变出现在不同的综合征中，表明不同的临床外显率和表达，相同的临床综合征中发现不同的基因突变，表明遗传异质性。
