Expanding the Phenotype of PPP1R21-Related Neurodevelopmental Disorder

Authors

Mohammed Almannai
Dana Marafi
Maha S Zaki
Reza Maroofian
Stephanie Efthymiou
Nebal Waill Saadi
Bilal Filimban
Hormos Salimi Dafsari
Fatima Rahman
Shazia Maqbool
Eissa Faqeih
Fuad Al Mutairi
Hind Alsharhan
Omar Abdelaty
Saadoun Bin-Hasan
Ruizhi Duan
Mahmoud M Noureldeen
Alaa Alqattan
Henry Houlden
Jill V Hunter
Jennifer E Posey
James R Lupski
Ayman W El-Hattab

Language

English

Publication Date

6-1-2024

Journal

Clinical Genetics

DOI

10.1111/cge.14492

PMID

38356149

PMCID

PMC11065596

PubMedCentral® Posted Date

6-1-2025

PubMedCentral® Full Text Version

Author MSS

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.

Keywords

Adolescent, Child, Child, Preschool, Female, Humans, Infant, Male, Brain, Developmental Disabilities, Genetic Association Studies, Genetic Predisposition to Disease, Intellectual Disability, Mutation, Neurodevelopmental Disorders, Pedigree, Phenotype, PPP1R21, neurodevelopmental disorders (NDD), autosomal recessive (AR) trait, consanguinity

Published Open-Access

yes

Recommended Citation

Almannai, Mohammed; Marafi, Dana; Zaki, Maha S; et al., "Expanding the Phenotype of PPP1R21-Related Neurodevelopmental Disorder" (2024). Faculty and Staff Publications. 5063.
https://digitalcommons.library.tmc.edu/baylor_docs/5063