Title | Expanding the phenotype of PPP1R21-related neurodevelopmental disorder. |
Publication Type | Journal Article |
Year of Publication | 2024 |
Authors | Almannai, M, Marafi, D, Zaki, MS, Maroofian, R, Efthymiou, S, Saadi, NWaill, Filimban, B, Dafsari, HSalimi, Rahman, F, Maqbool, S, Faqeih, E, Mutairi, FAl, Alsharhan, H, Abdelaty, O, Bin-Hasan, S, Duan, R, Noureldeen, MM, Alqattan, A, Houlden, H, Hunter, JV, Posey, JE, Lupski, JR, El-Hattab, AW |
Journal | Clin Genet |
Volume | 105 |
Issue | 6 |
Pagination | 620-629 |
Date Published | 2024 Jun |
ISSN | 1399-0004 |
Keywords | Adolescent, Brain, Child, Child, Preschool, Developmental Disabilities, Female, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Infant, Intellectual Disability, Male, Mutation, Neurodevelopmental Disorders, Pedigree, Phenotype |
Abstract | PPP1R21 encodes for a conserved protein that is involved in endosomal maturation. Biallelic pathogenic variants in PPP1R21 have been associated with a syndromic neurodevelopmental disorder from studying 13 affected individuals. In this report, we present 11 additional individuals from nine unrelated families and their clinical, radiological, and molecular findings. We identified eight different variants in PPP1R21, of which six were novel variants. Global developmental delay and hypotonia are neurological features that were observed in all individuals. There is also a similar pattern of dysmorphic features with coarse faces as a gestalt observed in several individuals. Common findings in 75% of individuals with available brain imaging include delays in myelination, wavy outline of the bodies of the lateral ventricles, and slight prominence of the bodies of the lateral ventricles. PPP1R21-related neurodevelopmental disorder is associated with a consistent phenotype and should be considered in highly consanguineous individuals presenting with developmental delay/intellectual disability along with coarse facial features. |
DOI | 10.1111/cge.14492 |
Alternate Journal | Clin Genet |
PubMed ID | 38356149 |
PubMed Central ID | PMC11065596 |
Grant List | T32 GM007526 / GM / NIGMS NIH HHS / United States UM1 HG006542 / HG / NHGRI NIH HHS / United States R35 NS105078 / NS / NINDS NIH HHS / United States K08 HG008986 / HG / NHGRI NIH HHS / United States WT093205MA / WT_ / Wellcome Trust / United Kingdom WT104033AIA / WT_ / Wellcome Trust / United Kingdom R01 GM106373 / GM / NIGMS NIH HHS / United States / WT_ / Wellcome Trust / United Kingdom U01 HG011758 / HG / NHGRI NIH HHS / United States |
Expanding the phenotype of PPP1R21-related neurodevelopmental disorder.
Similar Publications
PRL1 and PRL3 promote macropinocytosis via its lipid phosphatase activity. Theranostics. 2024;14(9):3423-3438. | .
Unveiling novel genetic variants in 370 challenging medically relevant genes using the long read sequencing data of 41 samples from 19 global populations. Mol Genet Genomics. 2024;299(1):65. | .
Genetic diversity of 1,845 rhesus macaques improves genetic variation interpretation and identifies disease models. Nat Commun. 2024;15(1):5658. | .