R Sakka, H Marmouch, M Trabelsi, A Achour, M Golli, I Hannachi, E Kerkeni, K Monastiri, F Maazoul, R M'rad
Research Unit of Congenital Anomalies and Childhood Cancer LR12SP13, Fattouma Bourguiba University Hospital of Monastir, University of Monastir, Tunisia.
Department of Internal Medicine and Endocrinology, Fattouma Bourguiba University Hospital, Monastir, Tunisia.
Eur J Med Genet. 2021 Feb;64(2):104138. doi: 10.1016/j.ejmg.2021.104138. Epub 2021 Jan 8.
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.
伴有A型脂肪营养不良的下颌骨发育不全是一种罕见的常染色体隐性疾病，其特征为颅面畸形、A型脂肪营养不良、锁骨发育不全和肢端溶解。它由LMNA基因的纯合或复合杂合错义突变引起。我们报告了5名突尼斯患者，他们在LMNA基因中携带相同的纯合c.1580G>A；p.(Arg527His)突变。这些患者表现出下颌骨发育不全的典型特征，包括眼球突出、鼻瘦或呈喙状、牙齿拥挤、下颌发育不全、手指远端指骨短而宽且尖端圆钝以及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-表型相关性研究发现，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，这些氨基酸位于A型核纤层蛋白C末端球状结构域内蛋白质功能的关键位点区域。此外，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替代类型。
