دورية أكاديمية
Phenotypic and molecular characterisation of CDK13-related congenital heart defects, dysmorphic facial features and intellectual developmental disorders
| العنوان: | Phenotypic and molecular characterisation of CDK13-related congenital heart defects, dysmorphic facial features and intellectual developmental disorders |
|---|---|
| المؤلفون: | Bostwick, Bret L, McLean, Scott, Posey, Jennifer E, Streff, Haley E, Gripp, Karen W, Blesson, Alyssa, Powell-Hamilton, Nina, Tusi, Jessica, Stevenson, David A, Farrelly, Ellyn, Hudgins, Louanne, Yang, Yaping, Xia, Fan, Wang, Xia, Liu, Pengfei, Walkiewicz, Magdalena, McGuire, Marianne, Grange, Dorothy K, Andrews, Marisa V, Hummel, Marybeth, Madan-Khetarpal, Suneeta, Infante, Elena, Coban-Akdemir, Zeynep, Miszalski-Jamka, Karol, Jefferies, John L, Rosenfeld, Jill A, Emrick, Lisa, Nugent, Kimberly M, Lupski, James R, Belmont, John W, Lee, Brendan, Lalani, Seema R |
| المصدر: | Faculty & Staff Scholarship |
| بيانات النشر: | The Research Repository @ WVU |
| سنة النشر: | 2017 |
| المجموعة: | The Research Repository @ WVU (West Virginia University) |
| الوصف: | Background: De novo missense variants in CDK13 have been described as the cause of syndromic congenital heart defects in seven individuals ascertained from a large congenital cardiovascular malformations cohort. We aimed to further define the phenotypic and molecular spectrum of this newly described disorder. Methods: To minimise ascertainment bias, we recruited nine additional individuals with CDK13 pathogenic variants from clinical and research exome laboratory sequencing cohorts. Each individual underwent dysmorphology exam and comprehensive medical history review. Results: We demonstrate greater than expected phenotypic heterogeneity, including 33% (3/9) of individuals without structural heart disease on echocardiogram. There was a high penetrance for a unique constellation of facial dysmorphism and global developmental delay, as well as less frequently seen renal and sacral anomalies. Two individuals had novel CDK13 variants (p.Asn842Asp, p.Lys734Glu), while the remaining seven unrelated individuals had a recurrent, previously published p.Asn842Ser variant. Summary of all variants published to date demonstrates apparent restriction of pathogenic variants to the protein kinase domain with clustering in the ATP and magnesium binding sites. Conclusions: Here we provide detailed phenotypic and molecular characterisation of individuals with pathogenic variants in CDK13 and propose management guidelines based upon the estimated prevalence of anomalies identified. Keywords: CDK13, CHDFIDD, De novo variant, Neurodevelopmental disorders, Agenesis of the corpus callosum, Hypertelorism, Developmental delay, Cyclin-dependent kinase, Undiagnosed Diseases Network |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | https://researchrepository.wvu.edu/faculty_publications/1477Test; https://researchrepository.wvu.edu/cgi/viewcontent.cgi?article=2498&context=faculty_publicationsTest |
| الإتاحة: | https://researchrepository.wvu.edu/faculty_publications/1477Test https://researchrepository.wvu.edu/cgi/viewcontent.cgi?article=2498&context=faculty_publicationsTest |
| رقم الانضمام: | edsbas.8F4AFCFC |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |