Further delineation of van den Ende-Gupta syndrome: Genetic heterogeneity and overlap with congenital heart defects and skeletal malformations syndrome.

Autor:	Hildebrandt CC; Genetics Unit, MassGeneral Hospital for Children, Massachusetts, USA.; Boston Children's Hospital Medical Biochemical Fellowship, Boston, Massachusetts, USA., Patel N; Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Graham JM Jr; Medical Genetics, Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, California, USA.; Department of Pediatrics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, USA., Bamshad M; Division of Genetic Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington, USA.; Department of Genome Sciences, University of Washington, Seattle, Washington, USA.; Brotman Baty Institute, Seattle, Washington, USA., Nickerson DA; Department of Genome Sciences, University of Washington, Seattle, Washington, USA.; Brotman Baty Institute, Seattle, Washington, USA., White JJ; Brotman Baty Institute, Seattle, Washington, USA., Marvin CT; Division of Genetic Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington, USA., Miller DE; Division of Genetic Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington, USA.; Department of Genome Sciences, University of Washington, Seattle, Washington, USA., Grand KL; Medical Genetics, Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, California, USA., Sanchez-Lara PA; Medical Genetics, Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, California, USA.; Department of Pediatrics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, USA., Schweitzer D; Division of Pediatric Genetics, Department of Pediatrics, University of California Los Angeles, Los Angeles, California, USA., Al-Zaidan HI; Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Al Masseri Z; Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Alkuraya FS; Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.; Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia., Lin AE; Genetics Unit, MassGeneral Hospital for Children, Massachusetts, USA.
Jazyk:	angličtina
Zdroj:	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.
DOI:	10.1002/ajmg.a.62194
Abstrakt:	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. (© 2021 Wiley Periodicals LLC.)
Databáze:	MEDLINE
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