Makri Samira, Clarke Nigel F, Richard Pascale, Maugenre Svetlana, Demay Laurence, Bonne Gisèle, Guicheney Pascale
Etablissement Hospitalier Spécialisé Ali Ait Idir, Alger, Algeria.
Neuromuscul Disord. 2009 Jan;19(1):26-8. doi: 10.1016/j.nmd.2008.09.016. Epub 2008 Dec 11.
Life-threatening cardiac and respiratory complications are common in LMNA-related myopathies and early diagnosis is important for optimal patient care. Lamin A/C related congenital muscular dystrophy (L-CMD) is often caused by de novo mutation in LMNA, affecting a single child in a family. Germinal mosaicism is a rarer variant that can lead to two children inheriting the same new heterozygous mutation from a clinically unaffected parent. Both patterns mimic autosomal recessive (AR) inheritance and the possibility of de novo L-CMD may be forgotten since most causes of congenital muscular dystrophy follow AR inheritance. To illustrate the challenge of diagnosing L-CMD, we present a consanguineous family in which two children have early onset LMNA-related myopathy likely due to paternal germinal mosaicism. This emphasises that germinal mosaicism (and de novo mutations) for LMNA can arise in any family and direct gene sequencing is required to confirm or exclude the diagnosis.
危及生命的心脏和呼吸并发症在与LMNA相关的肌病中很常见，早期诊断对于患者的最佳治疗至关重要。与核纤层蛋白A/C相关的先天性肌营养不良（L-CMD）通常由LMNA中的新发突变引起，影响家族中的单个儿童。生殖系嵌合是一种较罕见的变异，可导致两个孩子从临床未受影响的父母那里继承相同的新杂合突变。这两种模式都模仿常染色体隐性（AR）遗传，由于大多数先天性肌营养不良的病因遵循AR遗传，新发L-CMD的可能性可能会被遗忘。为了说明诊断L-CMD的挑战，我们展示了一个近亲家庭，其中两个孩子患有可能由于父系生殖系嵌合而导致的早发性与LMNA相关的肌病。这强调了LMNA的生殖系嵌合（和新发突变）可出现在任何家庭中，需要直接进行基因测序以确认或排除诊断。
