Clinical and molecular description of 19 patients with GATAD2B-Associated Neurodevelopmental Disorder (GAND).

Details

Serval ID
serval:BIB_0C00C80EBBDF
Type
Article: article from journal or magazin.
Publication sub-type
Case report (case report): feedback on an observation with a short commentary.
Collection
Publications
Institution
Title
Clinical and molecular description of 19 patients with GATAD2B-Associated Neurodevelopmental Disorder (GAND).
Journal
European journal of medical genetics
Author(s)
Vera G., Sorlin A., Delplancq G., Lecoquierre F., Brasseur-Daudruy M., Petit F., Smol T., Ziegler A., Bonneau D., Colin E., Mercier S., Cogné B., Bézieau S., Edery P., Lesca G., Chatron N., Sabatier I., Duban-Bedu B., Colson C., Piton A., Durand B., Capri Y., Perrin L., Wiesener A., Zweier C., Maroofian R., Carroll C.J., Galehdari H., Mazaheri N., Callewaert B., Giulianno F., Zaafrane-Khachnaoui K., Buchert-Lo R., Haack T., Magg J., Rieß A., Blandfort M., Waldmüller S., Horber V., Leonardi E., Polli R., Turolla L., Murgia A., Frebourg T., Lebre A.S., Nicolas G., Saugier-Veber P., Guerrot A.M.
ISSN
1878-0849 (Electronic)
ISSN-L
1769-7212
Publication state
Published
Issued date
10/2020
Peer-reviewed
Oui
Volume
63
Number
10
Pages
104004
Language
english
Notes
Publication types: Case Reports ; Journal Article
Publication Status: ppublish
Abstract
De novo pathogenic variants in the GATAD2B gene have been associated with a syndromic neurodevelopmental disorder (GAND) characterized by severe intellectual disability (ID), impaired speech, childhood hypotonia, and dysmorphic features. Since its first description in 2013, nine patients have been reported in case reports and a series of 50 patients was recently published, which is consistent with the relative frequency of GATAD2B pathogenic variants in public databases. We report the detailed phenotype of 19 patients from various ethnic backgrounds with confirmed pathogenic GATAD2B variants including intragenic deletions. All individuals presented developmental delay with a median age of 2.5 years for independent walking and of 3 years for first spoken words. GATAD2B variant carriers showed very little subsequent speech progress, two patients over 30 years of age remaining non-verbal. ID was mostly moderate to severe, with one profound and one mild case, which shows a wider spectrum of disease severity than previously reported. We confirm macrocephaly as a major feature in GAND (53%). Most common dysmorphic features included broad forehead, deeply set eyes, hypertelorism, wide nasal base, and pointed chin. Conversely, prenatal abnormalities, non-cerebral malformations, epilepsy, and autistic behavior were uncommon. Other features included feeding difficulties, behavioral abnormalities, and unspecific abnormalities on brain MRI. Improving our knowledge of the clinical phenotype is essential for correct interpretation of the molecular results and accurate patient management.
Keywords
Adolescent, Adult, Brain/diagnostic imaging, Brain/pathology, Child, Child, Preschool, Face/pathology, Female, GATA Transcription Factors/genetics, High-Throughput Nucleotide Sequencing, Humans, Infant, Intellectual Disability/diagnosis, Intellectual Disability/diagnostic imaging, Intellectual Disability/genetics, Magnetic Resonance Imaging, Male, Megalencephaly/diagnostic imaging, Megalencephaly/genetics, Muscle Hypotonia/genetics, Neurodevelopmental Disorders/diagnosis, Neurodevelopmental Disorders/diagnostic imaging, Neurodevelopmental Disorders/genetics, Neurodevelopmental Disorders/physiopathology, Phenotype, Pregnancy, Repressor Proteins, Sequence Deletion, Speech Disorders/genetics, Developmental delay, GATAD2B, Intellectual disability, Next-generation sequencing
Pubmed
Web of science
Open Access
Yes
Create date
24/07/2020 14:06
Last modification date
13/04/2024 7:05
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