Youssefian Leila, Vahidnezhad Hassan, Daneshpazhooh Maryam, Abdollahzadeh Sina, Talari Hamidreza, Khoshnevisan Alireza, Chams-Davatchi Cheyda, Mobasher Roozbeh, Li Qiaoli, Uitto Jouni, Akhondzadeh Shahin, Tabrizi Mina
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Dermatology and Cutaneous Biology, The Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Exp Dermatol. 2015 Mar;24(3):220-2. doi: 10.1111/exd.12620.
Lipoid proteinosis (LP) is a rare autosomal recessive genodermatosis caused by loss-of-function mutations in the ECM1 gene, and previous studies have noted phenotypic variability. In this study, we examined 12 patients representing three Iranian families for clinical manifestations and genotyped them for mutations in ECM1. LP was diagnosed with characteristic mucocutaneous and neurologic manifestations. Five patients were also subjected to magnetic resonance imaging (MRI)/computed tomography (CT) scan of the central nervous system. DNA was isolated from peripheral blood from patients and their clinically unaffected relatives, and mutations in ECM1 were sought by PCR-based amplification of all exons and flanking intronic sequences, followed by bidirectional Sanger sequencing. Significant phenotypic variability in this multisystem disorder, including presence of convulsions and epilepsy in about half of the patients was noted. In most cases, this was associated with calcifications in the brain detected by MRI/CT scans. Genotyping of the affected individuals in three families from the central region of Iran revealed presence of homozygous c.507delT mutation in ECM1, reflecting the observed consanguinity in these families. This large cohort revealed extensive phenotypic variability in individuals with the same mutation in ECM1. This observation suggests a role for genetic and epigenetic as well as environmental modulation of the phenotype. Identification of mutations allows screening of unaffected individuals for presence or absence of this mutation in extended LP families, with implications for genetic counseling.
类脂蛋白沉积症（LP）是一种由ECM1基因功能丧失性突变引起的罕见常染色体隐性遗传性皮肤病，先前的研究已注意到其表型变异性。在本研究中，我们检查了代表三个伊朗家庭的12名患者的临床表现，并对他们的ECM1基因突变进行了基因分型。LP根据典型的皮肤黏膜和神经系统表现进行诊断。5名患者还接受了中枢神经系统的磁共振成像（MRI）/计算机断层扫描（CT）。从患者及其临床未受影响的亲属的外周血中分离DNA，通过基于PCR的所有外显子和侧翼内含子序列扩增寻找ECM1突变，随后进行双向桑格测序分析。注意到这种多系统疾病存在显著的表型变异性，约一半患者存在惊厥和癫痫。在大多数情况下，这与MRI/CT扫描检测到的脑部钙化有关。对来自伊朗中部地区三个家庭的受影响个体进行基因分型，发现ECM1中存在纯合的c.507delT突变，这反映了这些家庭中观察到的近亲结婚情况。这个大型队列研究揭示了具有相同ECM1突变的个体存在广泛的表型变异性。这一观察结果表明基因、表观遗传以及环境对表型的调节作用。突变的鉴定能够在扩大的LP家系中对未受影响个体进行该突变是否存在的筛查，这对遗传咨询具有重要意义。
