MARBACH, Felix; LIPSKA-ZIETKIEWICZ, Beata S.; KNUROWSKA, Agata; MICHAUD, Vincent; MARGOT, Henri; LESPINASSE, James; TRAN MAU THEM, Frederic; COUBES, Christine; PARK, Joohyun; GROSCH, Sarah; ROGGIA, Cristiana; GRASSHOFF, Ute; KALSNER, Louisa; DENOMME-PICHON, Anne-Sophie; AFENJAR, Alexandra; HERON, Benedicte; KEREN, Boris; CARO, Pilar; SCHAAF, Christian P.

doi:10.1002/ajmg.a.62884

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American Journal of Medical Genetics Part A. 2022-09, vol. 188, n° 9, p. 2627-2636

Résumé en anglais

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.< Réduire

Mots clés en anglais

Autism spectrum disorder

Global developmental delay

Neurodevelopmental disorder

Pain insensitivity

PRKAR1B

Protein kinase a complex

URI

https://oskar-bordeaux.fr/handle/20.500.12278/170059

DOI

http://dx.doi.org/10.1002/ajmg.a.62884

Unités de recherche

Maladies Rares : Génétique et Métabolisme (MRGM) - UMR 1211

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Phenotypic characterization of seven individuals with Marbach-Schaaf neurodevelopmental syndrome

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Mots clés en anglais

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