Mandibuloacral dysplasia with type A lipodystrophy is a rare autosomal recessive disorder characterized by craniofacial dysmorphism, type A lipodystrophy, clavicular dysplasia, and acroostelolysis. It is caused by homozygous or compound heterozygous missense mutations in LMNA gene. We report five Tunisian patients harboring the same homozygous c.1580G > A; p. (Arg527His) mutation in LMNA gene. The patients presented with typical features of mandibuloacral dysplasia including, prominent eyes, thin or beaked nose, dental overcrowding, mandibular hypoplasia, short and broad finger's distal phalanges with round tips and lipodystrophy type A. Newly recognized signs are growth hormone deficiency and dilated cardiomyopathy. Genotype-phenotype correlation found that at least one of the disease's LMNA mutant alleles involve one of the highly conserved aminoacids, residing in a key site domain for protein function within the C-terminal globular domain of A-type lamins. Also, the severity of the disease depends on the position in the protein's domain and on the type of substitution of the concerned aminoacid.

伴A型脂肪营养不良的下颌骨发育不良是一种罕见的常染色体隐性遗传疾病，其特征为颅面畸形，A型脂肪营养不良，锁骨发育不良和肢端骨溶解。它是由LMNA基因中的纯合或复合杂合错义突变引起的。我们报告了5名突尼斯患者携带相同的纯合子c.1580G> A；p。LMNA中的（Arg527His）突变基因。患者表现出典型的下颌骨发育不良特征，包括突出的眼睛，稀薄的鼻子或尖锐的鼻子，牙齿过度拥挤，下颌发育不全，短而宽的手指远端指尖（圆尖）和A型脂肪营养不良。新发现的体征是生长激素缺乏和扩张型心肌病。基因型与表型的相关性发现，该疾病的LMNA突变等位基因中至少有一个涉及高度保守的氨基酸之一，位于A型lamins C端球形结构域内蛋白质功能的关键位点域中。同样，疾病的严重程度取决于蛋白质结构域中的位置以及相关氨基酸的取代类型。