Back to Search
Start Over
Further delineation of van den Ende-Gupta syndrome: Genetic heterogeneity and overlap with congenital heart defects and skeletal malformations syndrome.
- Source :
-
American journal of medical genetics. Part A [Am J Med Genet A] 2021 Jul; Vol. 185 (7), pp. 2136-2149. Date of Electronic Publication: 2021 Mar 30. - Publication Year :
- 2021
-
Abstract
- Van den Ende-Gupta syndrome (VDEGS) is a rare autosomal recessive condition characterized by distinctive facial and skeletal features, and in most affected persons, by biallelic pathogenic variants in SCARF2. We review the type and frequency of the clinical features in 36 reported individuals with features of VDEGS, 15 (42%) of whom had known pathogenic variants in SCARF2, 6 (16%) with negative SCARF2 testing, and 15 (42%) not tested. We also report three new individuals with pathogenic variants in SCARF2 and clinical features of VDEGS. Of the six persons without known pathogenic variants in SCARF2, three remain unsolved despite extensive genetic testing. Three were found to have pathogenic ABL1 variants using whole exome sequencing (WES) or whole genome sequencing (WGS). Their phenotype was consistent with the congenital heart disease and skeletal malformations syndrome (CHDSKM), which has been associated with ABL1 variants. Of the three unsolved cases, two were brothers who underwent WGS and targeted long-range sequencing of both SCARF2 and ABL1, and the third person who underwent WES and RNA sequencing for SCARF2. Because these affected individuals with classical features of VDEGS lacked a detectable pathogenic SCARF2 variant, genetic heterogeneity is likely. Our study shows the importance of performing genetic testing on individuals with the VDEGS "phenotype," either as a targeted gene analysis (SCARF2, ABL1) or WES/WGS. Additionally, individuals with the combination of arachnodactyly and blepharophimosis should undergo echocardiography while awaiting results of molecular testing due to the overlapping physical features of VDEGS and CHDSKM.<br /> (© 2021 Wiley Periodicals LLC.)
- Subjects :
- Abnormalities, Multiple pathology
Adolescent
Adult
Arachnodactyly pathology
Blepharophimosis pathology
Child
Child, Preschool
Contracture pathology
Female
Genes, Recessive genetics
Genetic Heterogeneity
Genetic Predisposition to Disease
Heart Defects, Congenital pathology
Humans
Infant
Male
Middle Aged
Exome Sequencing
Young Adult
Abnormalities, Multiple genetics
Arachnodactyly genetics
Blepharophimosis genetics
Contracture genetics
Heart Defects, Congenital genetics
Proto-Oncogene Proteins c-abl genetics
Scavenger Receptors, Class F genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1552-4833
- Volume :
- 185
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- American journal of medical genetics. Part A
- Publication Type :
- Report
- Accession number :
- 33783941
- Full Text :
- https://doi.org/10.1002/ajmg.a.62194