Growth, development, and phenotypic spectrum of individuals with deletions of 2q33.1 involving SATB2


Por: Zarate YA, Bosanko KA, Thomas MA, Miller DT, Cusmano-Ozog K, Martinez-Monseny T, Curry CJ, Graham JM Jr, Velsher L, Bekheirnia MR, Seidel V, Dedousis D, Mitchell AL, DiMarino AM, Riess A, Balasubramanian M, Fish JL, Caffrey AR, Fleischer N, Pierson TM and Lacro RV

Publicada: 1 abr 2021 Ahead of Print: 1 ene 2021
Resumen:
SATB2-Associated syndrome (SAS) is an autosomal dominant, multisystemic, neurodevelopmental disorder due to alterations in SATB2 at 2q33.1. A limited number of individuals with 2q33.1 contiguous deletions encompassing SATB2 (Delta SAS) have been described in the literature. We describe 17 additional individuals with Delta SAS, review the phenotype of 33 previously published individuals with 2q33.1 deletions (n = 50, mean age = 8.5 +/- 7.8 years), and provide a comprehensive comparison to individuals with other molecular mechanisms that result in SAS (non-Delta SAS). Individuals in the Delta SAS group were often underweight for age (20/41 = 49%) with a progressive decline in weight (95% CI = -2.3 to -1.1, p < 0.0001) and height (95% CI = -2.3 to -1.0, p < 0.0001) Z-score means from birth to last available measurement. Delta SAS individuals were often noted to have a broad spectrum of facial dysmorphism. A composite image of Delta SAS individuals generated by automated image analysis was distinct as compared to matched controls and non-Delta SAS individuals. We also present additional genotype-phenotype correlations for individuals in the Delta SAS group such as an increased risk for aortic root/ascending aorta dilation and primary pulmonary hypertension for those individuals with contiguous gene deletions that include COL3A1/COL5A2 and BMPR2, respectively. Based on these findings, we provide additional care recommendations for individuals with Delta SAS variants.

Filiaciones:
Zarate YA:
 Section of Genetics and Metabolism, University of Arkansas for Medical Sciences, Little Rock, AR, USA

Bosanko KA:
 Section of Genetics and Metabolism, University of Arkansas for Medical Sciences, Little Rock, AR, USA

Thomas MA:
 Departments of Medical Genetics and Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

Miller DT:
 Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA

Cusmano-Ozog K:
 Department of Pathology, Stanford University Medical Center, Stanford, CA, USA

Martinez-Monseny T:
 Department of Clinical Genetics and Rare Disease Paediatric Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain

Curry CJ:
 Genetic Medicine, Department of Pediatrics, University of California, Fresno, CA, USA

Graham JM Jr:
 Medical Genetics, Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA, USA

Velsher L:
 North York General, Toronto, Canada

Bekheirnia MR:
 Departments of Pediatrics and Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA

Seidel V:
 Clinical Genetics, Department of Pediatrics, HGU Gregorio Marañón, Madrid, Spain

Dedousis D:
 University Hospitals Center for Human Genetics, Cleveland, OH, USA

Mitchell AL:
 University Hospitals Center for Human Genetics, Cleveland, OH, USA

DiMarino AM:
 UH Rainbow Babies and Children's Hospital, Cleveland, OH, USA

Riess A:
 Institute of Medical Genetics and Applied Genomics, Tuebingen, Germany

Balasubramanian M:
 Sheffield Clinical Genetics Service, Sheffield, UK

Fish JL:
 Department of Biological Sciences, University of Massachusetts Lowell, Lowell, Massachusetts

Caffrey AR:
 Health Outcomes, College of Pharmacy, University of Rhode Island, Kingston, RI, USA

Fleischer N:
 FDNA Inc, Boston, MA, USA

Pierson TM:
 Departments of Pediatrics and Neurology & The Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA

Lacro RV:
 Department of Cardiology, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA, USA
ISSN: 00099163





CLINICAL GENETICS
Editorial
WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ, Dinamarca
Tipo de documento: Article
Volumen: 99 Número: 4
Páginas: 547-557
WOS Id: 000607380200001
ID de PubMed: 33381861
imagen Green Accepted

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