| Autor: |
Megan Yabumoto, Jessica Kianmahd, Meghna Singh, Maria F. Palafox, Angela Wei, Kathryn Elliott, Dana H. Goodloe, S. Joy Dean, Catherine Gooch, Brianna K. Murray, Erin Swartz, Samantha A. Schrier Vergano, Meghan C. Towne, Kimberly Nugent, Elizabeth R. Roeder, Christina Kresge, Beth A. Pletcher, Katheryn Grand, John M. Graham Jr., Ryan Gates, Natalia Gomez‐Ospina, Subhadra Ramanathan, Robin Dawn Clark, Kimberly Glaser, Paul J. Benke, Julie S. Cohen, Ali Fatemi, Weiyi Mu, Kristin W. Baranano, Jill A. Madden, Cynthia S. Gubbels, Timothy W. Yu, Pankaj B. Agrawal, Mary‐Kathryn Chambers, Chanika Phornphutkul, John A. Pugh, Kate A. Tauber, Svetlana Azova, Jessica R. Smith, Anne O’Donnell‐Luria, Hannah Medsker, Siddharth Srivastava, Deborah Krakow, Daniela N. Schweitzer, Valerie A. Arboleda |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Molecular Genetics & Genomic Medicine, Vol 9, Iss 10, Pp n/a-n/a (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2324-9269 |
| DOI: |
10.1002/mgg3.1809 |
| Popis: |
Abstract The phenotypic variability associated with pathogenic variants in Lysine Acetyltransferase 6B (KAT6B, a.k.a. MORF, MYST4) results in several interrelated syndromes including Say‐Barber‐Biesecker‐Young‐Simpson Syndrome and Genitopatellar Syndrome. Here we present 20 new cases representing 10 novel KAT6B variants. These patients exhibit a range of clinical phenotypes including intellectual disability, mobility and language difficulties, craniofacial dysmorphology, and skeletal anomalies. Given the range of features previously described for KAT6B‐related syndromes, we have identified additional phenotypes including concern for keratoconus, sensitivity to light or noise, recurring infections, and fractures in greater numbers than previously reported. We surveyed clinicians to qualitatively assess the ways families engage with genetic counselors upon diagnosis. We found that 56% (10/18) of individuals receive diagnoses before the age of 2 years (median age = 1.96 years), making it challenging to address future complications with limited accessible information and vast phenotypic severity. We used CRISPR to introduce truncating variants into the KAT6B gene in model cell lines and performed chromatin accessibility and transcriptome sequencing to identify key dysregulated pathways. This study expands the clinical spectrum and addresses the challenges to management and genetic counseling for patients with KAT6B‐related disorders. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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