Expanded phenotypic spectrum of UDP-glucose-6-dehydrogenase recessive neurodevelopmental disorder: Two novel descriptions with or without epileptic encephalopathy.

Autor: Bordeneuve-Plante P; CHU Lille, Institut de Génétique Médicale, Lille, France., Boussion S; Univ. Lille, ULR7364 - RADEME - Maladies RAres du Developpement embryonnaire et du Métabolisme, Lille, France.; CHU Lille, Clinique de Génétique, CRMR Déficiences Intellectuelles de Causes Rares, Lille, France., Rama M; CHU Lille, Institut de Génétique Médicale, Lille, France., Brunelle P; CHU Lille, Institut de Génétique Médicale, Lille, France.; Univ. Lille, ULR7364 - RADEME - Maladies RAres du Developpement embryonnaire et du Métabolisme, Lille, France., Thuillier C; CHU Lille, Institut de Génétique Médicale, Lille, France., Vanlerberghe C; Univ. Lille, ULR7364 - RADEME - Maladies RAres du Developpement embryonnaire et du Métabolisme, Lille, France.; CHU Lille, Clinique de Génétique, CRMR Déficiences Intellectuelles de Causes Rares, Lille, France., Caumes R; Univ. Lille, ULR7364 - RADEME - Maladies RAres du Developpement embryonnaire et du Métabolisme, Lille, France.; CHU Lille, Clinique de Génétique, CRMR Déficiences Intellectuelles de Causes Rares, Lille, France., Colson C; Univ. Lille, ULR7364 - RADEME - Maladies RAres du Developpement embryonnaire et du Métabolisme, Lille, France.; CHU Lille, Clinique de Génétique, CRMR Déficiences Intellectuelles de Causes Rares, Lille, France., Ait-Yahya E; CHU Lille, Unité de Bio-informatique, Plateau de Biologie-Moléculaire, Lille, France., Ghoumid J; Univ. Lille, ULR7364 - RADEME - Maladies RAres du Developpement embryonnaire et du Métabolisme, Lille, France.; CHU Lille, Clinique de Génétique, CRMR Déficiences Intellectuelles de Causes Rares, Lille, France., Smol T; CHU Lille, Institut de Génétique Médicale, Lille, France.; Univ. Lille, ULR7364 - RADEME - Maladies RAres du Developpement embryonnaire et du Métabolisme, Lille, France.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2024 Jul 12, pp. e63820. Date of Electronic Publication: 2024 Jul 12.
DOI: 10.1002/ajmg.a.63820
Abstrakt: Recent advances in the understanding of infantile developmental epileptic encephalopathies (IDEE) have revealed the association of biallelic pathogenic variants in UGDH. In this study, we report two novel combinations identified by exome sequencing: p.(Arg135Trp) with p.(Arg65*) and p.(Arg102Trp) with p.(Arg65*). Both combinations share a common pathogenic nonsense variant, with the missense variants strategically located in the NAD-binding domain of the UGDH protein, predicted in structural models to create new interactions with the central domain. The first patient exhibited the typical UGDH-related disease phenotype and progressive microcephaly, a rarely reported feature. In contrast, the second patient presented an atypical phenotype, including absence of seizure, severe intellectual disability, ataxic gait, and abnormal eye movements. This comprehensive analysis extends the phenotypic spectrum of UGDH syndrome beyond early infantile intractable encephalopathy to include intellectual disability without epilepsy.
(© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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