Mandibuloacral Dysplasia Caused by LMNA Mutations and Uniparental Disomy.
Mandibuloacral Dysplasia Caused by LMNA Mutations and Uniparental Disomy.
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DOI：
10.1155/2014/508231
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发表时间：
2014
影响因子：
--
通讯作者：
Das S
中科院分区：
文献类型：
--
作者：
Bai S;Lozada A;Jones MC;Dietz HC;Dempsey M;Das S
下颌骨肢端发育不良（MAD）是一种罕见的常染色体隐性遗传疾病，其特征是出生后生长迟缓，颅面畸形，骨骼畸形和斑驳的皮肤色素沉着。Hutchinson-Gilford早衰综合征（HGPS）是以儿童期加速衰老为特征的临床疾病。MAD和HGPS都可以由LMNA基因突变引起。在这项研究中，我们描述了一个2岁的男孩与重叠功能的MAD和HGPS。LMNA基因的突变分析揭示了一个纯合错义变化，p.M540T，而只有母亲携带突变。对1号染色体的单亲二体性（UPD）分析显示存在母体UPD。在LMNA基因座侧翼的1q21.3-q22区域中的标记是等二体的，而在短臂和远端1 q区域中的标记是异二体的。这些结果表明，在母体减数分裂不分离，随后在三体挽救过程中丢失的父亲1号染色体可能会导致在该患者中观察到的p.M540T突变的p.M540T 1和纯合性。
Mandibuloacral dysplasia (MAD) is a rare autosomal recessive disorder characterized by postnatal growth retardation, craniofacial anomalies, skeletal malformations, and mottled cutaneous pigmentation. Hutchinson-Gilford Progeria Syndrome (HGPS) is characterized by the clinical features of accelerated aging in childhood. Both MAD and HGPS can be caused by mutations in the LMNA gene. In this study, we describe a 2-year-old boy with overlapping features of MAD and HGPS. Mutation analysis of the LMNA gene revealed a homozygous missense change, p.M540T, while only the mother carries the mutation. Uniparental disomy (UPD) analysis for chromosome 1 showed the presence of maternal UPD. Markers in the 1q21.3–q22 region flanking the LMNA locus were isodisomic, while markers in the short arm and distal 1q region were heterodisomic. These results suggest that nondisjunction in maternal meiosis followed by loss of the paternal chromosome 1 during trisomy rescue might result in the UPD1 and homozygosity for the p.M540T mutation observed in this patient.