■Dysferlinopathies代表一组肢带或远端肌营养不良,具有常染色体-隐性遗传模式,这是由于在dysferlin基因(DYSF)中存在致病性变体所致。
■在这项工作中,我们描述了一个来自巴西一个小城市的人群,该人群携带DYSF的c.5979dupA致病变种,可导致肢带肌营养不良2R型和远端肌营养不良。
使用与在DYSF中分析的具有重复的区域互补的定制探针,通过qPCR进行基因分型分析。
■共检查了104个人。在48例(46.15%)个体中鉴定出c.5979dupA。23个(22%)是纯合子,其中13人(56.5%)为女性。共有91.3%(21)的纯合子个体有阳性家族史,七人(30.4%)报告有近亲婚姻。25(24%)个体为同一变异的杂合(25.8±16岁),其中15人(60%)为女性。纯合子的平均CK水平为697IU,杂合子为140.5IU,野生型同合子为176IU。弱点分布模式显示17.3%的个体具有近端模式,13%为远端模式,69.6%为混合模式。疲劳存在于15个纯合子和一个杂合子中。
■这种变体在这个小社区的个体中的高流行率可以通过与历史相关的可能的创始人效应来解释,地理和文化方面。
UNASSIGNED: Dysferlinopathies represent a group of limb girdle or distal muscular dystrophies with an autosomal-recessive inheritance pattern resulting from the presence of pathogenic variants in the dysferlin gene (DYSF).
UNASSIGNED: In this work, we describe a population from a small city in Brazil carrying the c.5979dupA pathogenic variant of DYSF responsible for limb girdle muscular dystrophy type 2R and distal muscular dystrophy.
UNASSIGNED: Genotyping analyses were performed by qPCR using customized probe complementary to the region with the duplication under analysis in the DYSF.
UNASSIGNED: A total of 104 individuals were examined. c.5979dupA was identified in 48 (46.15%) individuals. Twenty-three (22%) were homozygotes, among whom 13 (56.5%) were female. A total of 91.3% (21) of homozygous individuals had a positive family history, and seven (30.4%) reported consanguineous marriages. Twenty-five (24%) individuals were heterozygous (25.8±16 years) for the same variant, among whom 15 (60%) were female. The mean CK level was 697 IU for homozygotes, 140.5 IU for heterozygotes and 176 IU for wild-type homo-zygotes. The weakness distribution pattern showed 17.3% of individuals with a proximal pattern, 13% with a distal pattern and 69.6% with a mixed pattern. Fatigue was present in 15 homozygotes and one heterozygote.
UNASSIGNED: The high prevalence of this variant in individuals from this small community can be explained by a possible founder effect associated with historical, geographical and cultural aspects.