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 |
Date Published | 2024 Feb 14 |
ISSN | 1399-0004 |
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 |
Grant List | UM1 HG006542 / HG / NHGRI NIH HHS / United States U01 HG011758 / HG / NHGRI NIH HHS / United States K08 HG008986 / HG / NHGRI NIH HHS / United States WT093205MA / WT_ / Wellcome Trust / United Kingdom WT104033AIA / WT_ / Wellcome Trust / United Kingdom |