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Objective To report the genetic analysis of a family with a fetus suspected of Ellis-van Creveld (EVC) syndrome based on ultrasound findings such as ventricular septal defect (VSD), short long bones in the limbs and polydactyly, and to conduct a literature review to clarify the pathogenic cause. Methods A 27-year-old pregnant woman, who was pregnant for the first time and had no prior deliveries, was admitted to the prenatal diagnosis center of Shijiazhuang Obstetrics and Gynecology Hospital in October 2021. At 17 weeks of gestation, ultrasound detected multiple fetal malformations. The genomic DNA of the fetal proband's amniotic fluid cells and the parents' peripheral blood samples were sequentially subjected to chromosomal karyotype analysis, chromosomal microarray analysis (CMA), and whole exome sequencing (WES). Suspected pathogenic mutations were verified by Sanger sequencing in the proband and its parents. Subsequently, a Minigene in vitro experiment was used to analyze one splicing mutation. Meanwhile, databases such as PubMed were searched, and literature reports were combined for genetic analysis. Results Chromosomal karyotype analysis of the fetus showed no abnormalities, and CMA did not detect any copy number variation (CNV) with clinical significance. WES results revealed two mutations in the EVC gene (NM_153717.2) of the fetus: a nonsense mutation c.1405G>T(p.E469X) in exon 10 and a splicing mutation c.1886+5G>A in intron 13. Family verification using Sanger sequencing showed that the father was a carrier of the c.1405G>T(p.E469X) mutation in exon 10, and the mother was a carrier of the c.1886+5G>A mutation in intron 13. The compound heterozygous mutation of the fetus was inherited from the parents. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG) for classifying genetic variations, c.1405G>T (p.E469X) was classified as likely pathogenic mutation (PVS1+PM2), and c.1886+5G>A was classified as likely pathogenic mutation (PM2+PM3_Strong). The Minigene experiment results showed that the c.1886+5G>A mutation caused a 115-bp segment retention in intron 13, further supporting its pathogenicity. Review of the literature showed that the typical clinical manifestations of EVC syndrome include short limbs, short ribs, postaxial polydactyly, nail and tooth dysplasia, and congenital heart defects. Gene mutations in EVC/EVC2 were found to be the main pathogenic cause through whole exome sequencing, with mutation types including missense mutations, large-scale duplications/deletions, in-frame microdeletions, nonsense mutations, frameshift mutations, and splicing mutations. Conclusions The compound heterozygous mutations in the EVC gene are the pathogenic cause of the fetus. The detection of these mutations expands the genetic variation spectrum of Ellis-van Creveld syndrome.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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