Tan Maria Melinda, Dy Jeanne Barbara, Salcedo-Arellano Maria Jimena, Tassone Flora, Hagerman Randi J
Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis Health, Sacramento, CA, USA.
MedMom Institute for Human Development, Pasig City, Philippines.
Future Neurol. 2019 May;14(2). doi: 10.2217/fnl-2018-0040. Epub 2019 May 24.
Mutations in the Fragile X Mental Retardation 1 () gene create a spectrum of developmental disorders in children in addition to neurodegenerative problems in older populations. Two types of mutations are recognized in the gene. The full mutation (>200 CGG repeats) in the gene leads to Fragile X Syndrome which is the most common inherited cause of intellectual disability and autism, while the premutation (55 to 200 CGG repeats) identified among carriers leads to a range of problems linked to elevated levels of the mRNA leading to mRNA toxicity and occasionally mildly deficient FMRP levels. Two disorders among premutation carriers have been recognized namely: the Fragile X-associated Primary Ovarian Insufficiency (FXPOI) and Fragile X-associated Tremor/Ataxia Syndrome (FXTAS). Recently, in order to recognize a group of associated disorders commonly found in premutation carriers and extensively reported in co-morbidities studies, a new distinctive name was proposed: Fragile X-associated Neuropsychiatric Disorders (FXAND). This paper will present a case report of a female premutation carrier who has encountered predominantly psychiatric problems, but also chronic pain and sleep disturbances consistent with FXAND.
脆性X智力低下1（FMR1）基因的突变除了会导致老年人群出现神经退行性问题外，还会在儿童中引发一系列发育障碍。FMR1基因存在两种类型的突变。该基因的完全突变（>200个CGG重复序列）会导致脆性X综合征，这是智力残疾和自闭症最常见的遗传病因，而携带者中鉴定出的前突变（55至200个CGG重复序列）会导致一系列与FMR1 mRNA水平升高相关的问题，进而导致mRNA毒性，偶尔还会出现FMRP水平轻度不足。前突变携带者中已确认有两种疾病，即脆性X相关原发性卵巢功能不全（FXPOI）和脆性X相关震颤/共济失调综合征（FXTAS）。最近，为了识别一组在前突变携带者中常见且在共病研究中有广泛报道的相关疾病，人们提出了一个新的独特名称：脆性X相关神经精神疾病（FXAND）。本文将呈现一例女性前突变携带者的病例报告，该患者主要出现了精神问题，但也有与FXAND相符的慢性疼痛和睡眠障碍。
