Quantitative Phenotype Morbidity Description of SATB2-Associated Syndrome
Journal
Human Mutation
ISSN
1098-1004
Date Issued
2023
Author(s)
Yuri A. Zarate
Katherine Bosanko
Amrit Kannan
Ashlen Thomason
Beth Nutt
Nihit Kumar
Kirt Simmons
Aaron Hiegert
Larry Hartzell
Adam Johnson
Tabitha Prater
Tobias Brünger
Arthur Stefanski
Dennis Lal
Aisling R. Caffrey
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:p>Characterized by developmental delay with severe speech delay, dental anomalies, cleft palate, skeletal abnormalities, and behavioral difficulties, SATB2-associated syndrome (SAS) is caused by pathogenic variants in SATB2. The SAS phenotype range of severity has been documented previously in large series. Using data from the SAS registry, we present the SAS severity score, a comprehensive scoring rubric that encompasses 15 different individual neurodevelopmental and systemic features. Higher (more severe) systemic and total (sum of neurodevelopmental and systemic scores) scores were seen for null variants located after amino acid 350 (the start of the CUT1 domain), the recurrent missense Arg389Cys variant (<jats:inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M1">
<mi>n</mi>
<mo>=</mo>
<mn>10</mn>
</math>
</jats:inline-formula>), intragenic deletions, and larger chromosomal deletions. The Arg389Cys variant had the highest cognitive, verbal, and sialorrhea severity scores, while large chromosomal deletions had the highest expressive, ambulation, palate, feeding and growth, neurodevelopmental, and total scores. Missense variants not located in the CUT1 or CUT2 domain scored lower in several subcategories. We conclude that the SAS severity score allows quantitative phenotype morbidity description that can be used in routine clinical counseling. Further refinement and validation of the SAS severity score are expected over time. All data from this project can be interactively explored in a new portal.</jats:p>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M1">
<mi>n</mi>
<mo>=</mo>
<mn>10</mn>
</math>
</jats:inline-formula>), intragenic deletions, and larger chromosomal deletions. The Arg389Cys variant had the highest cognitive, verbal, and sialorrhea severity scores, while large chromosomal deletions had the highest expressive, ambulation, palate, feeding and growth, neurodevelopmental, and total scores. Missense variants not located in the CUT1 or CUT2 domain scored lower in several subcategories. We conclude that the SAS severity score allows quantitative phenotype morbidity description that can be used in routine clinical counseling. Further refinement and validation of the SAS severity score are expected over time. All data from this project can be interactively explored in a new portal.</jats:p>
Cite this document
Zarate, Y. A., Bosanko, K., Kannan, A., Thomason, A., Nutt, B., Kumar, N., Simmons, K., Hiegert, A., Hartzell, L., Johnson, A., Prater, T., Pérez-Palma, E., Brünger, T., Stefanski, A., Lal, D., & Caffrey, A. R. (2023). Quantitative phenotype morbidity description of satb2-associated syndrome. Human Mutation, 2023, 1-9. https://doi.org/10.1155/2023/8200176
Subjects
adolescent
;
adult
;
article
;
autosomal dominant disorder
;
child
;
chromosome aberration
;
chromosome deletion
;
cleft palate
;
clinical article
;
developmental delay
;
dna binding
;
female
;
human
;
hypersalivation
;
literacy
;
male
;
morbidity
;
phenotype
;
preschool child
;
satb2 associated syndrome
;
school child
;
skeleton malformation
;
speech delay
;
tooth malformation
;
young adult