A De Novo Nonsense Mutation in MAGEL2 in a Patient Initially Diagnosed as Opitz-C: Similarities Between Schaaf-Yang and Opitz-C Syndromes
A De Novo Nonsense Mutation in MAGEL2 in a Patient Initially Diagnosed as Opitz-C: Similarities Between Schaaf-Yang and Opitz-C Syndromes
复制标题
最初诊断为 Opitz-C 的患者中 MAGEL2 的新生无义突变：Schaaf-Yang 和 Opitz-C 综合征之间的相似之处
作者：
R. Urreizti;A. Cueto;Héctor Franco;Sílvia Mort;Neus Roca;Julia Ponomarenko;L. Cozzuto;Carlos Company;Mattia Bosio;S. Ossowski;M. Montfort;J. Hecht;E. Tizzano;B. Cormand;L. Vilageliu;J. M. Opitz;G. Neri;D. Grinberg;S. Balcells
奥皮茨三角头综合征（OTCS）是一种罕见的遗传性疾病，其特征是颅面畸形，可变的智力和精神残疾，以及可变的心脏缺陷，死亡率高。在这种综合征中已知不同的遗传模式和遗传异质性。一名最初诊断为OTCS的19岁女孩（P7）的全外显子组和基因组测序显示，MAGEL 2基因中存在一个从头无义突变p.Q638*。MAGEL 2是一个位于Prader-Willi区域15 q11 -13的印记，母系沉默的基因。患者P7在父亲染色体中携带突变。最近，MAGEL 2的突变已被描述为Schaaf-Yang综合征（SHFYNG）和严重关节弯曲症。患者P7与SHFYNG病例相似，但具有该综合征中未描述的其他发现，而在OTCS中常见。我们对另外9名OTCS患者的MAGEL 2基因进行了测序，没有发现突变。这项研究为OTCS病例提供了第一个明确的分子遗传学基础，表明OTCS和SHFYNG综合征之间存在重叠，并证实OTCS是遗传异质性的。编码MAGEL 2伴侣的基因，无论是在逆行转运还是在泛素化-去泛素化复合物中，都是OTCS致病基因的有希望的候选者。
Opitz trigonocephaly C syndrome (OTCS) is a rare genetic disorder characterized by craniofacial anomalies, variable intellectual and psychomotor disability, and variable cardiac defects with a high mortality rate. Different patterns of inheritance and genetic heterogeneity are known in this syndrome. Whole exome and genome sequencing of a 19-year-old girl (P7), initially diagnosed with OTCS, revealed a de novo nonsense mutation, p.Q638*, in the MAGEL2 gene. MAGEL2 is an imprinted, maternally silenced, gene located at 15q11-13, within the Prader-Willi region. Patient P7 carried the mutation in the paternal chromosome. Recently, mutations in MAGEL2 have been described in Schaaf-Yang syndrome (SHFYNG) and in severe arthrogryposis. Patient P7 bears resemblances with SHFYNG cases but has other findings not described in this syndrome and common in OTCS. We sequenced MAGEL2 in nine additional OTCS patients and no mutations were found. This study provides the first clear molecular genetic basis for an OTCS case, indicates that there is overlap between OTCS and SHFYNG syndromes, and confirms that OTCS is genetically heterogeneous. Genes encoding MAGEL2 partners, either in the retrograde transport or in the ubiquitination-deubiquitination complexes, are promising candidates as OTCS disease-causing genes.
影响因子：
16
作者：
Hao YH;Fountain MD Jr;Fon Tacer K;Xia F;Bi W;Kang SH;Patel A;Rosenfeld JA;Le Caignec C;Isidor B;Krantz ID;Noon SE;Pfotenhauer JP;Morgan TM;Moran R;Pedersen RC;Saenz MS;Schaaf CP;Potts PR
通讯作者：
Potts PR
影响因子：
4
作者：
Tidyman, William E.;Rauen, Katherine A.
通讯作者：
Rauen, Katherine A.