Sewairi Wafaa, Assiri Abdulrahman, Patel Nisha, Alhashem Amal, Alkuraya Fowzan S
Department of Pediatrics, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
Eur J Hum Genet. 2016 Aug;24(8):1220-2. doi: 10.1038/ejhg.2015.265. Epub 2016 Jan 6.
LMNA encodes lamin A and lamin C, two major components of the nuclear lamina, and its pathogenic variants lead to a dozen distinct clinical entities collectively known as laminopathies. Most LMNA-related laminopathies are autosomal dominant but four are autosomal recessive; furthermore, some of the dominant variants have been associated with distinct phenotypes when inherited recessively, further complicating the ability to correlate genotype with phenotype. We report a consanguineous family in which the index presented with an apparently unique constellation of poikiloderma, joint motion restriction and distal acroosteolysis but lacks features of muscle weakness, lipodystrophy, or cardiac or craniofacial involvement. Molecular analysis revealed the presence of a novel homozygous LMNA missense variant (NM_170707.3:c.1774G>A; p.(Gly592Arg)) within an area of autozygome that is not shared by his unaffected siblings. The proposed causal link is further supported by in silico analysis of this variant. Our case suggests an expansion of LMNA allelic disorders to include distal acroosteolysis, poikiloderma and joint stiffness (DAPJ).
LMNA基因编码核纤层蛋白A和核纤层蛋白C，这是核纤层的两个主要成分，其致病性变异会导致十几种不同的临床病症，统称为核纤层蛋白病。大多数与LMNA相关的核纤层蛋白病是常染色体显性遗传，但有四种是常染色体隐性遗传；此外，一些显性变异在隐性遗传时与不同的表型相关，这使得将基因型与表型相关联的能力更加复杂。我们报告了一个近亲家庭，其中先证者表现出一组明显独特的皮肤异色症、关节活动受限和远端肢端骨质溶解症状，但没有肌肉无力、脂肪代谢障碍或心脏或颅面受累的特征。分子分析显示，在其未受影响的兄弟姐妹未共享的纯合子区域内存在一种新的LMNA错义变异（NM_170707.3:c.1774G>A；p.(Gly592Arg)）。对该变异的计算机模拟分析进一步支持了所提出的因果关系。我们的病例表明，LMNA等位基因疾病范围扩大，包括远端肢端骨质溶解、皮肤异色症和关节僵硬（DAPJ）。
