Nguyen Tran Quynh Nhu, Saitoh Makiko, Trinh Huu Tung, Doan Nguyen Minh Thien, Mizuno Yoko, Seki Masafumi, Sato Yusuke, Ogawa Seishi, Mizuguchi Masashi
Department of Developmental Medical Sciences, School of International Health, Graduate School of Medicine, The University of Tokyo, Kyoto, Japan.
Children's Hospital 2, Ho Chi Minh City, Vietnam.
Congenit Anom (Kyoto). 2016 Sep;56(5):209-16. doi: 10.1111/cga.12155.
Ellis-van Creveld syndrome (EvC) is a ciliopathy with cardiac anomalies, disproportionate short stature, polydactyly, dystrophic nails and oral defects. To obtain further insight into the genetics of EvC, we screened EVC/EVC2 mutations in eight Vietnamese EvC patients. All the patients had a congenital heart defect with atypical oral and/or skeletal abnormalities. One had compound heterozygous EVC2 mutations: a novel mutation c.769G > T-p.E177X in exon 6 inherited from father and another previously reported c.2476C > T-p.R826X mutation in exon 14 inherited from mother. The EVC2 mRNA expression level was significantly lower in the patient and her parents compared to controls. Another case had a novel heterozygous EVC mutation (c.1717C > G-p.S572X) in exon 12, inherited from his father. Of note, the mother without any EVC mutation on Sanger sequencing showed a lower expression level of EVC mRNA compared with controls. SNP array analysis revealed that the patient and mother had a heterozygous 16.4 kb deletion in EVC. This patient also had a heterozygous novel variant in exon 9 of EFCAB7 (c.1171 T > C-p.Y391H), inherited from his father. The atypical cardiac phenotype of this patient and the father suggested that EFCAB7 may modify the phenotype by interacting with EVC. In conclusion, we detected two novel nonsense mutations and a partial deletion of EVC/EVC2 in two Vietnamese families with EvC. Moreover, we found in one family a missense mutation of EFCAB7, a possible modifier gene in EvC and its related disorders.
埃利斯-范克里维尔德综合征（EvC）是一种伴有心脏异常、身材比例失调性矮小、多指畸形、指甲营养不良和口腔缺陷的纤毛病。为了进一步深入了解EvC的遗传学，我们对8名越南EvC患者进行了EVC/EVC2突变筛查。所有患者均有先天性心脏缺陷，并伴有非典型口腔和/或骨骼异常。一名患者有复合杂合性EVC2突变：从父亲遗传的外显子6中的新突变c.769G＞T-p.E177X，以及从母亲遗传的外显子14中先前报道的c.2476C＞T-p.R826X突变。与对照组相比，该患者及其父母的EVC2 mRNA表达水平显著降低。另一例患者在外显子12中有一个新的杂合性EVC突变（c.1717C＞G-p.S572X），从其父亲遗传而来。值得注意的是，经桑格测序未发现任何EVC突变的母亲，其EVC mRNA表达水平与对照组相比也较低。单核苷酸多态性阵列分析显示，该患者和母亲在EVC中有一个16.4 kb的杂合性缺失。该患者在EFCAB7的外显子9中也有一个从父亲遗传而来的杂合性新变异（c.1171T＞C-p.Y391H）。该患者及其父亲的非典型心脏表型表明，EFCAB7可能通过与EVC相互作用来修饰表型。总之，我们在两个患有EvC的越南家庭中检测到两个新的无义突变以及EVC/EVC2的部分缺失。此外，我们在一个家庭中发现了EFCAB7的错义突变，它可能是EvC及其相关疾病中的一个修饰基因。
