Title: Truncation and microdeletion of EVC accompanied by with a novel EFCAB7 missense mutation inn Ellis-Van Creveld syndrome with atypical rare syndromic congenital heart defects: Ellis-Van Creveld syndromeCongenital heart disorder is a high risk of developmental disabilities.
First author: Tran QuynhNhu Nguyen1,3
Co-author: Makiko Saitoh1,2, Huu Tung Trinh3, Nguyen Minh Thien Doan4, Yoko Mizuno2 Masafumi Seki2, Yusuke Sato5, Seishi Ogawa5 and Masashi Mizuguchi1,2
1Department of Developmental Medical Sciences, School of International Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
2Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
3Children’s Hospital 2, Ho Chi Minh City, Vietnam
4 Department of General Internal Medicine, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam
5Department of Pathology and tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Ellis-van Creveld syndrome (EvC)belongs tois a ciliopathy with cardiac anomalies, disproportionate short stature, polydactyly, dystrophic nails and oral defects. Approximately 60% of EvC patients had have severe congenital heart defecisorderts (CHDs), in of which more than half are atrio-ventricular septal defect (AVSD) and common atrium, which leads to early childhood mortality. Neuropsychological development of EvC is generally normal. However, CHD was confirmed as a high risk of developmental disabilities (DDs). Here we presented a typical EvC case with DDs. She is a 2.5-year-old female, the first child of consanguineous couple. Here height was 62.0 cm (under the 2nd percentile), post-axial polydactyly of hands, nail dystrophy, and AVSD with pulmonary stenosis. Her SPO2 was 70-80% from birth. We detected two novel compound heterozygous variants (p. E177X, p.R826X) in this patient. Her mental development was normal up to the age of 2 years old. From 2 to 2 ½ years-old, she reveals DDs, which was evaluate by ASQ-3 score. The head circumference is 47.0 cm. MRI showed no defects. We suggested that hypoxia caused DDs in this patient.
DDs in children with CHD are common and should be alert. The feeding difficulty, hypoxia, medical comorbidities, genetic abnormalities, and more complex treatment increased risk for DD. Thus, longitudinal follow-up throughout childhood and into adulthood is necessary for children with CHD because exposure to risk and prevalence of DD change over time. Primary and special care for children with CHD is critical to minimize DDs. (233 words)In However, the EvC phenotype overlaps with other ciliopathies, which hampers the accurate diagnosis. In this study, we reported one EvC Vietnamese EvC-family with an atypical CHD phenotype (, short chordalis). A 32-month-old boy had a novel heterozygous EVC mutation (c.1717C>G-p.S572X) in exon 12, inherited from his father who hadse phenotype was milder phenotype than his son’s. Of note, the mother without any EVC mutation noran EvC phenotype 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 16kb deletion in EVC, started and ended-breakpoints were inranging from intron 9 and to intron 11. As the patient and the father had an atypical CHD, In addition, as the patient and his father had atypical EvC-CHD (short chordalis), we hypothesized that it co-existed another genetic changes. wThus, we screened EFCAB7 and IQCE as the candidate for the modifiers of EvC phenotype. EFCAB7 and IQCE are ciliary proteins, which positively regulates the Hh pathway and anchor the EVC-EVC2 complex in a signaling microdomain at the base of cilia. EvC gene. A novel missense mutation c.1171T>C-p. in EFCAB7 was found in the patient and the father. This mutation located in a possible binding site of EFCAB7 and EVC2. With regard to the father with a heterozygous EVC mutation, this EFCAB7 mutation may have played a role in the pathogenesis of atypical EvC-like disorder consisting of short stature and short chordalis. Taken together, Wwe, and may have modified the EvC phenotype in this family. Our findings suggested the physiological role of EFCAB7 in cardiac development and a mutation of EFCAB7, as well as its pathogenetic role as a might modifyier in EvC phenotype and related disorders. (249 229words)
Biography
NGUYEN Tran QuynhNhu Nguyen graduated from University of Medicine and Pharmacy, Ho Chi Minh city, Vietnam in 2007. Since 2008, she has worked as cardiologist in Children’s Hospital 2, Ho Chi Minh city, Vietnam. She has completed master course from School of Medicine, The University of Tokyo, Japan in March 2015 and now continues Ph.D course at the same above university.
Presenting author details
Full name: NGUYENguyen Tran QuynhNhu
Contact number: +81 8062537292
Session name/ number:Pediatric neurology/ Track 18Pediatric Cardiology/ Track 9
Category: Oral presentation