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Hildebrand, M.S.* ; Braden, R.O.* ; Lauretta, M.L.* ; Kaspi, A.* ; Leventer, R.J.* ; Anderson, M.C.* ; Goel, H.* ; Bahlo, M.* ; Scheffer, I.E.* ; Amor, D.J.* ; Janowski, R. ; Niessing, D. ; Morgan, A.T.*

Inherited PURA pathogenic variant associated with a mild neurodevelopmental disorder.

Neurol. Genet. 10:e200181 (2024)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
OBJECTIVES: Purine-rich element-binding protein alpha (PURA) regulates gene expression and is ubiquitously expressed with an enrichment in neural tissues. Pathogenic variants in PURA cause the neurodevelopmental disorder PURA syndrome that has a variable phenotype but typically comprises moderate-to-severe global developmental delay, intellectual disability, early-onset hypotonia and hypothermia, epilepsy, feeding difficulties, movement disorders, and subtle facial dysmorphism. Speech is reportedly absent in most, but the specific linguistic phenotype is not well described. METHODS: We used genome sequencing to identify a pathogenic gene variant as part of a study of children ascertained for severe primary speech disorder in the absence of moderate or severe ID. RESULTS: The novel PURA c.296G>T (p.Arg99Leu) pathogenic missense variant segregated in the female proband and her affected mother. The proband had dysarthria; phonological disorder; and severe receptive and expressive language impairment, borderline intellect, attention difficulties, oropharyngeal dysmotility, and dysmorphic facial features. Her mother had dysarthria, moderate receptive language impairment, and borderline intellect. Both the proband and her mother completed mainstream schooling with classroom support. DISCUSSION: This is the first inherited PURA pathogenic germline variant in over 600 unrelated families documented on ClinVar or reported in the literature. PURA testing should be considered in families with primary speech disorder and borderline intellectual disability, given the specific genetic counseling implications.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Phenotype
ISSN (print) / ISBN 2376-7839
e-ISSN 2376-7839
Zeitschrift Neurology Genetics
Quellenangaben Band: 10, Heft: 5, Seiten: , Artikelnummer: e200181 Supplement: ,
Verlag American Academy of Neurology
Verlagsort Minneapolis, Minn.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Structural Biology (STB)
Förderungen NHMRC Centre of Research Excellence Translational Centre for Speech Disorders Grant
Science Award of the Care-for-Rare Foundation
NHMRC Investigator Grant