Back to Search
Start Over
Phenotypic characterization of seven individuals with <scp>Marbach–Schaaf</scp> neurodevelopmental syndrome
- Source :
- American Journal of Medical Genetics Part A, American Journal of Medical Genetics Part A, 2022, 188 (9), pp.2627-2636. ⟨10.1002/ajmg.a.62884⟩
- Publication Year :
- 2022
- Publisher :
- Wiley, 2022.
-
Abstract
- International audience; We present the phenotypes of seven previously unreported patients with Marbach-Schaaf neurodevelopmental syndrome, all carrying the same recurrent heterozygous missense variant c.1003C>T (p.Arg335Trp) in PRKAR1B. Clinical features of this cohort include global developmental delay and reduced sensitivity to pain, as well as behavioral anomalies. Only one of the seven patients reported here was formally diagnosed with autism spectrum disorder (ASD), while ASD-like features were described in others, overall indicating a lower prevalence of ASD in Marbach-Schaaf neurodevelopmental syndrome than previously assumed. The clinical spectrum of the current cohort is similar to that reported in the initial publication, delineating a complex developmental disorder with behavioral and neurologic features. PRKAR1B encodes the regulatory subunit R1beta of the protein kinase A complex (PKA), and is expressed in the adult and embryonal central nervous system in humans. PKA is crucial to a plethora of cellular signaling pathways, and its composition of different regulatory and catalytic subunits is cell-type specific. We discuss potential molecular disease mechanisms underlying the patients' phenotypes with respect to the different known functions of PKA in neurons, and the phenotypes of existing R1beta-deficient animal models.
- Subjects :
- Adult
Pain insensitivity
Autism Spectrum Disorder
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Global developmental delay
[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
[SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis
Syndrome
[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics
Cohort Studies
[SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis
Phenotype
Neurodevelopmental disorder
PRKAR1B
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
Neurodevelopmental Disorders
Genetics
Protein kinase a complex
Animals
Humans
Genetics (clinical)
Subjects
Details
- ISSN :
- 15524833 and 15524825
- Volume :
- 188
- Database :
- OpenAIRE
- Journal :
- American Journal of Medical Genetics Part A
- Accession number :
- edsair.doi.dedup.....e06efeca202ca317987da1f92ad2ee67