Delineating the Adult Phenotype of PGM2L1-Related Neurodevelopmental Disorder
Küçük Resim Yok
Tarih
2026
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Wiley
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
PGM2L1 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.
Açıklama
Anahtar Kelimeler
Neurodevelopmental Disorder, Renal Anomaly, Scoliosis, Tooth Loss
Kaynak
American Journal of Medical Genetics Part A
WoS Q Değeri
Q3
Scopus Q Değeri
Q3
Cilt
200
Sayı
3
