scholarly journals Loss of function mutation of mouse Snap29 on a mixed genetic background phenocopy abnormalities found in CEDNIK and 22q11.2 Deletion Syndrome patients

2019 ◽  
Author(s):  
Vafa Keser ◽  
Jean-François Boisclair Lachance ◽  
Sabrina Shameen Alam ◽  
Youngshin Lim ◽  
Eleonora Scarlata ◽  
...  
Keyword(s):  
Protein Trafficking ◽  
Genetic Background ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Skin Defect ◽  
Loss Of Function ◽  
22Q11.2 Deletion ◽  
Developmental Abnormalities ◽  
Mixed Genetic Background ◽  
Skin Abnormalities

AbstractSynaptosomal-associated protein 29 (SNAP29) is a member of the SNARE family of proteins involved in maintenance of various intracellular protein trafficking pathways. SNAP29 maps to the 22q11.2 region and is deleted in 90% of patients with 22q11.2 deletion syndrome (22q11.2DS). However, the contribution of hemizygosity of SNAP29 to developmental abnormalities in 22q11.2DS remains to be determined. Mutations in SNAP29 are responsible for the developmental syndrome called CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma). On an inbred C57Bl/6J genetic background, only the ichthyotic skin defect associated with CEDNIK was reported. In this study, we show that loss of function mutation of Snap29 on a mixed genetic background not only models skin abnormalities found in CEDNIK, but also phenocopy ophthalmological, neurological, and motor defects found in these patients and a subset of 22q11.2DS patients. Thus, our findings indicate that mouse models of human syndromes should be analyzed on a mixed genetic background. Our work also reveals an unanticipated requirement for Snap29 in male fertility, and support contribution of hemizygosity for SNAP29 to the phenotypic spectrum of abnormalities found in 22q11.2DS patients.

scholarly journals Snap29 mutant mice recapitulate neurological and ophthalmological abnormalities associated with 22q11 and CEDNIK syndrome

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Vafa Keser ◽  
Jean-François Boisclair Lachance ◽  
Sabrina Shameen Alam ◽  
Youngshin Lim ◽  
Eleonora Scarlata ◽  
...  
Keyword(s):  
Protein Trafficking ◽  
Male Fertility ◽  
Genetic Background ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Loss Of Function ◽  
Intracellular Protein ◽  
22Q11.2 Deletion ◽  
Phenotypic Spectrum ◽  
Skin Abnormalities

Abstract Synaptosomal-associated protein 29 (SNAP29) encodes a member of the SNARE family of proteins implicated in numerous intracellular protein trafficking pathways. SNAP29 maps to the 22q11.2 region and is deleted in 90% of patients with 22q11.2 deletion syndrome (22q11.2DS). Moreover, bi-allelic SNAP29 mutations in patients are responsible for CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma) syndrome. A mouse model that recapitulates abnormalities found in these syndromes is essential for uncovering the cellular basis of these disorders. In this study, we report that mice with a loss of function mutation of Snap29 on a mixed CD1;FvB genetic background recapitulate skin abnormalities associated with CEDNIK, and also phenocopy neurological and ophthalmological abnormalities found in CEDNIK and a subset of 22q11.2DS patients. Our work also reveals an unanticipated requirement for Snap29 in male fertility and supports contribution of hemizygosity for SNAP29 to the phenotypic spectrum of abnormalities found in 22q11.2DS patients.

scholarly journals Palatoschisis, Schizophrenia and Hypocalcaemia: Phenotypic Expression of 22q11.2 Deletion Syndrome (DiGeorge Syndrome) in an Adult

2021 ◽  
Author(s):  
Melissa Elise van der Meijs ◽  
Dave Henri Schweitzer ◽  
Henk Boom
Keyword(s):  
Digeorge Syndrome ◽  
Phenotypic Expression ◽  
22Q11.2 Deletion Syndrome ◽  
Clinical Findings ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Developmental Abnormalities ◽  
Congenital Cardiac Anomalies ◽  
History Of ◽  
Arch System

22q11.2 deletion syndrome typically presents with congenital cardiac anomalies, immunodeficiencies and hypoparathyroidism. However, clinical findings vary greatly. We present the case of a 56-year-old man, with a history of cleft palate and schizophrenia, who was newly diagnosed with 22q11.2 deletion syndrome during an episode of hypocalcaemia. The syndrome is caused by developmental abnormalities of the embryonic pharyngeal arch system. Treatment of hypocalcaemia with oral calcium and vitamin D is usually sufficient.

scholarly journals A higher rare CNV burden in the genetic background potentially contributes to intellectual disability phenotypes in 22q11.2 deletion syndrome

2018 ◽  
Vol 61 (4) ◽  
pp. 209-212 ◽  
Author(s):  
Matthew Jensen ◽  
R. Frank Kooy ◽  
Tony J. Simon ◽  
Edwin Reyniers ◽  
Santhosh Girirajan ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Genetic Background ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion

Surgical Management of Patients With 22q11.2 Deletion Syndrome

2019 ◽  
Vol 4 (5) ◽  
pp. 857-869
Author(s):  
Oksana A. Jackson ◽  
Alison E. Kaye
Keyword(s):  
Surgical Management ◽  
Preoperative Evaluation ◽  
Preoperative Assessment ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Surgical Decision ◽  
Obstructive Sleep ◽  
Spine Abnormalities ◽  
Speech Assessment

Purpose The purpose of this tutorial was to describe the surgical management of palate-related abnormalities associated with 22q11.2 deletion syndrome. Craniofacial differences in 22q11.2 deletion syndrome may include overt or occult clefting of the palate and/or lip along with oropharyngeal variances that may lead to velopharyngeal dysfunction. This chapter will describe these circumstances, including incidence, diagnosis, and indications for surgical intervention. Speech assessment and imaging of the velopharyngeal system will be discussed as it relates to preoperative evaluation and surgical decision making. Important for patients with 22q11.2 deletion syndrome is appropriate preoperative screening to assess for internal carotid artery positioning, cervical spine abnormalities, and obstructive sleep apnea. Timing of surgery as well as different techniques, common complications, and outcomes will also be discussed. Conclusion Management of velopharyngeal dysfunction in patients with 22q11.2 deletion syndrome is challenging and requires thoughtful preoperative assessment and planning as well as a careful surgical technique.

Psychosocial Risks and Management for Children and Adolescents With 22q11.2 Deletion Syndrome

2019 ◽  
Vol 4 (4) ◽  
pp. 633-640 ◽  
Author(s):  
Canice E. Crerand ◽  
Ari N. Rabkin
Keyword(s):  
Cognitive Abilities ◽  
Psychotic Disorders ◽  
Developmental Stages ◽  
Early Adulthood ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Psychosocial Risks ◽  
Empirically Supported ◽  
Specific Education

Purpose This article reviews the psychosocial risks associated with 22q11.2 deletion syndrome, a relatively common genetic condition associated with a range of physical and psychiatric problems. Risks associated with developmental stages from infancy through adolescence and early adulthood are described, including developmental, learning, and intellectual disabilities as well as psychiatric disorders including anxiety, mood, and psychotic disorders. Other risks related to coping with health problems and related treatments are also detailed for both affected individuals and their families. Conclusion The article ends with strategies for addressing psychosocial risks including provision of condition-specific education, enhancement of social support, routine assessment of cognitive abilities, regular mental health screening, and referrals for empirically supported psychiatric and psychological treatments.

Conotruncal heart defects and aortic arch anomalies in fetuses with 22q11.2 deletion syndrome

2020 ◽  
Author(s):  
I.V. Novikova, O.M. Khurs, T.V. Demidovich et all
Keyword(s):  
Aortic Arch ◽  
Heart Defects ◽  
22Q11.2 Deletion Syndrome ◽  
Ventricular Outflow Tract ◽  
Double Outlet Right Ventricle ◽  
Interrupted Aortic Arch ◽  
Left Ventricular ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Aortic Arch Anomalies

16 second trimester fetuses with 22q11.2 deletion syndrome have been examined at anatomic-pathological investigation. Main cardiovascular diseases were ascending aorta hypoplasia with aortic valve stenosis (n = 6; 37.5%), truncus arteriosus (n = 5; 31.25%), tetralogy of Fallot (n = 3; 18.75%) and double-outlet right ventricle (n = 1; 6.25%). Ventricular septal defect was present in 16 cases. Associated aortic arch anomalies included interrupted aortic arch (n = 9; 56.25%), right aortic arch (n = 6; 37.5%), retroesophageal ring (n = 1; 6.25%) and aberrant right subclavian arteria (n = 5; 31.25%). 5 fetuses had left ventricular outflow tract obstructive lesions with interrupted aortic arch of type B combined with aberrant right subclavian arteria.

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