PDF(Pubmed)
Abstract：
BACKGROUND: Mandibulofacial dysostosis with microcephaly (MFDM, OMIM# 610536) is a rare monogenic disease that is caused by a mutation in the elongation factor Tu GTP binding domain containing 2 gene (EFTUD2, OMIM* 603892). It is characterized by mandibulofacial dysplasia, microcephaly, malformed ears, cleft palate, growth and intellectual disability. MFDM can be easily misdiagnosed due to its phenotypic overlap with other craniofacial dysostosis syndromes. The clinical presentation of MFDM is highly variable among patients.
METHODS: A patient with craniofacial anomalies was enrolled and evaluated by a multidisciplinary team. To make a definitive diagnosis, whole-exome sequencing was performed, followed by validation by Sanger sequencing.
RESULTS: The patient presented with extensive facial bone dysostosis, upward slanting palpebral fissures, outer and middle ear malformation, a previously unreported orbit anomaly, and spina bifida occulta. A novel, pathogenic insertion mutation (c.215_216insT: p.Tyr73Valfs*4) in EFTUD2 was identified as the likely cause of the disease.
CONCLUSIONS: We diagnosed this atypical case of MFDM by the detection of a novel pathogenetic mutation in EFTUD2. We also observed previously unreported features. These findings enrich both the genotypic and phenotypic spectrum of MFDM.
METHODS: A patient with craniofacial anomalies was enrolled and evaluated by a multidisciplinary team. To make a definitive diagnosis, whole-exome sequencing was performed, followed by validation by Sanger sequencing.
RESULTS: The patient presented with extensive facial bone dysostosis, upward slanting palpebral fissures, outer and middle ear malformation, a previously unreported orbit anomaly, and spina bifida occulta. A novel, pathogenic insertion mutation (c.215_216insT: p.Tyr73Valfs*4) in EFTUD2 was identified as the likely cause of the disease.
CONCLUSIONS: We diagnosed this atypical case of MFDM by the detection of a novel pathogenetic mutation in EFTUD2. We also observed previously unreported features. These findings enrich both the genotypic and phenotypic spectrum of MFDM.
摘要：
背景：伴有小头畸形的下颌面骨发育不良（MFDM，OMIM＃610536）是一种罕见的单基因疾病，是由含有2基因的延伸因子TuGTP结合域中的突变引起的（EFTUD2，OMIM*603892）。它的特点是颌面发育不良，小头畸形,畸形的耳朵，腭裂,成长和智力残疾。MFDM由于其与其他颅面骨发育不良综合征的表型重叠，很容易被误诊。MFDM的临床表现在患者中是高度可变的。
方法：纳入一名颅面畸形患者，并由多学科小组进行评估。为了做出明确的诊断，进行了全外显子组测序,然后通过Sanger测序进行验证。
结果：患者表现为广泛的面部骨骨发育不全，向上倾斜的睑裂,外耳和中耳畸形，以前未报告的轨道异常，和隐性脊柱裂.一部小说,EFTUD2中的致病性插入突变（c.215_216insT：p.Tyr73Valfs*4）被确定为该疾病的可能原因。
结论：我们通过在EFTUD2中检测到一种新的致病突变来诊断这种不典型的MFDM病例。我们还观察到以前未报告的特征。这些发现丰富了MFDM的基因型和表型谱。
方法：纳入一名颅面畸形患者，并由多学科小组进行评估。为了做出明确的诊断，进行了全外显子组测序,然后通过Sanger测序进行验证。
结果：患者表现为广泛的面部骨骨发育不全，向上倾斜的睑裂,外耳和中耳畸形，以前未报告的轨道异常，和隐性脊柱裂.一部小说,EFTUD2中的致病性插入突变（c.215_216insT：p.Tyr73Valfs*4）被确定为该疾病的可能原因。
结论：我们通过在EFTUD2中检测到一种新的致病突变来诊断这种不典型的MFDM病例。我们还观察到以前未报告的特征。这些发现丰富了MFDM的基因型和表型谱。
