Delineating the Adult Phenotype of PGM2L1-Related Neurodevelopmental Disorder

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dc.contributor.authorErcoskun, Pelin
dc.contributor.authorAkbulut, Ekrem
dc.contributor.authorYavas, Cuneyd
dc.contributor.authorYilmaz Celik, Lale
dc.contributor.authorDogan, Mustafa
dc.date.accessioned2026-06-19T06:41:20Z
dc.date.available2026-06-19T06:41:20Z
dc.date.issued2026
dc.departmentMalatya Turgut Özal Üniversitesi
dc.description.abstractPGM2L1 is a crucial enzyme exhibiting glucose 1,6-bisphosphate synthase activity, with predominant expression in brain tissue. In 2021, biallelic pathogenic variants in the PGM2L1 gene were first linked to a neurodevelopmental disorder characterized primarily by developmental delay in four pediatric cases. In this study, we aimed to delineate the adult phenotype associated with the PGM2L1-related neurodevelopmental disorder and to perform functional characterization of the identified variant. Two siblings presenting with neurodevelopmental delay were evaluated clinically and genetically. Exome sequencing of the older sibling revealed a homozygous nonsense variant, c.277C>T p.(Gln73Ter), in the PGM2L1 gene. This variant results in truncation leading to loss of key functional domains including the substrate binding site, catalytic active site, and protein stability regions. Quantitative analysis demonstrated a significant reduction in PGM2L1 gene expression in both siblings compared to controls (p value < 0.01). Unlike previously reported pediatric cases, the second sibling exhibited additional features including scoliosis, renal anomaly, tooth loss, hypothyroidism, bladder trabeculation, anhidrosis, and temperature intolerance, notably in the absence of obesity. These cases represent the first detailed description of an adult phenotype associated with a biallelic pathogenic variant in PGM2L1, expanding the clinical spectrum of this neurodevelopmental disorder.
dc.identifier.doi10.1002/ajmg.a.64293
dc.identifier.endpage684
dc.identifier.issn1552-4825
dc.identifier.issn1552-4833
dc.identifier.issue3
dc.identifier.orcid0000-0003-0464-6565
dc.identifier.orcid0000-0002-7526-9835
dc.identifier.pmid41178743
dc.identifier.scopus2-s2.0-105020760699
dc.identifier.scopusqualityQ3
dc.identifier.startpage673
dc.identifier.urihttps://doi.org/10.1002/ajmg.a.64293
dc.identifier.urihttps://hdl.handle.net/20.500.12899/6197
dc.identifier.volume200
dc.identifier.wosWOS:001607335700001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherWiley
dc.relation.ispartofAmerican Journal of Medical Genetics Part A
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20260612
dc.subjectNeurodevelopmental Disorder
dc.subjectRenal Anomaly
dc.subjectScoliosis
dc.subjectTooth Loss
dc.titleDelineating the Adult Phenotype of PGM2L1-Related Neurodevelopmental Disorder
dc.typeArticle

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