Investigating the role of a novel hemizygous FAAH2 variant in neurological and metabolic disorders

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene Pub Date : 2025-07-29 DOI:10.1016/j.gene.2025.149703

Mirella Vinci , Donatella Greco , Simone Treccarichi , Antonino Musumeci , Angelo Gloria , Concetta Federico , Salvatore Saccone , Francesco Calì , Sandra Sirrs

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Abstract

Fatty acid amide hydrolase 2 (FAAH2) is an enzyme involved in the degradation of endocannabinoids in humans. Altered FAAH2 activity has been implicated in various neurological and psychiatric conditions. We describe a male patient presenting with anxiety disorder, autistic-like traits, and borderline intellectual functioning (BIF), as well as metabolic disturbances including obesity and hepatic steatosis. Trio-based whole-exome sequencing (WES) identified the novel hemizygous c.988C > A (p.Gln330Lys) variant in the X-linked FAAH2 gene, which currently lacks an associated MIM phenotype. Structural modelling suggested that the variant induces multiple alterations in the amidase signature (AS), a key functional domain of the enzyme. These findings contribute to the emerging evidence supporting FAAH2 as a candidate gene for a neurodevelopmental phenotype with metabolic involvement, consistent with an X-linked inheritance pattern.

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研究一种新的半合子FAAH2变异在神经和代谢疾病中的作用

脂肪酸酰胺水解酶2 （FAAH2）是一种参与人体内源性大麻素降解的酶。FAAH2活性的改变与各种神经和精神疾病有关。我们描述了一位男性患者表现出焦虑障碍，自闭症样特征，边缘性智力功能（BIF），以及代谢紊乱，包括肥胖和肝脂肪变性。三基全外显子组测序（WES）鉴定出新的半合子c.988C >；这是x连锁FAAH2基因中的一个（p.Gln330Lys）变异，目前缺乏相关的MIM表型。结构建模表明，该变异诱导了酰胺酶特征（AS）的多重改变，这是酶的一个关键功能域。这些发现有助于新出现的证据支持FAAH2作为与代谢相关的神经发育表型的候选基因，与x连锁遗传模式一致。

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来源期刊

Gene 生物-遗传学

CiteScore

6.10

自引率

2.90%

发文量

718

审稿时长

42 days

期刊介绍： Gene publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses.