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Phenotypic characterization of seven individuals with Marbach–Schaaf neurodevelopmental syndrome
Author(s) -
Marbach Felix,
LipskaZiętkiewicz Beata S.,
Knurowska Agata,
Michaud Vincent,
Margot Henri,
Lespinasse James,
Tran Mau Them Frédéric,
Coubes Christine,
Park Joohyun,
Grosch Sarah,
Roggia Cristiana,
Grasshoff Ute,
Kalsner Louisa,
DenomméPichon AnneSophie,
Afenjar Alexandra,
Héron Bénédicte,
Keren Boris,
Caro Pilar,
Schaaf Christian P.
Publication year - 2022
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.62884
Subject(s) - autism spectrum disorder , neurodevelopmental disorder , phenotype , cohort , autism , protein subunit , missense mutation , neuroscience , medicine , biology , genetics , psychiatry , gene
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 R1β 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 R1β‐deficient animal models.