Fragile X syndrome (FXS) is a cognitive disorder caused by silencing of the fragile X mental retardation 1 gene (FMR1). Absence of the associated protein FMRP leads to the dysregulation of many genes creating a phenotype of ADHD, anxiety, epilepsy and autism.There are also several physical features commonly associated with FXS, including elongated faces, prominent ears, and macroorchidism. The most prevalent genetic aberration at the FMR1 locus arises from a noncoding CGG repeat in the 5'untranslated region.
Category
Chromosomal abnormality
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Chromosomal anomalies, excluding gene mutations
Sex chromosome anomalies
LD55 Fragile X chromosome
H00465 Fragile X syndrome
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06541 Cytoskeleton in neurons
H00465 Fragile X syndrome
See also H01731 Fragile X tremor/ataxia syndrome (FXTAS).
(FXR) Full mutation expansions (>200 CGG repeats)
(FXTAS) Smaller expansions in the premutation range (55-200 CGG repeats)
Napoli I, Mercaldo V, Boyl PP, Eleuteri B, Zalfa F, De Rubeis S, Di Marino D, Mohr E, Massimi M, Falconi M, Witke W, Costa-Mattioli M, Sonenberg N, Achsel T, Bagni C
Title
The fragile X syndrome protein represses activity-dependent translation through CYFIP1, a new 4E-BP.
Premature ovarian failure (POF) is characterized by amenorrhea before the age of 40 years with elevated levels of gonadotrophin (LH and FSH) and low levels of gonadal hormones (estrogens and inhibins). The causes of POF can be categorized into genetic and environmental mechanisms. X chromosome defects such as Turner syndrome or trisomy X as well as many genes including BMP15 andFMR1 are associated with POF development. For the environmental causes, medical intervention including surgeries and chemotherapies may lead to POF. Autoimmune ovarian failure consists another large category of POF.
Category
Reproductive system disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
16 Diseases of the genitourinary system
Diseases of the female genital system
GA30 Menopausal or certain specified perimenopausal disorders
H00627 Premature ovarian failure
Pathway-based classification of diseases [BR:br08402]
Replication and repair
nt06506 Double-strand break repair
H00627 Premature ovarian failure
nt06508 Interstrand crosslink repair
H00627 Premature ovarian failure
Cellular process
nt06523 Epigenetic regulation by Polycomb complexes
H00627 Premature ovarian failure
nt06541 Cytoskeleton in neurons
H00627 Premature ovarian failure
Bione S, Sala C, Manzini C, Arrigo G, Zuffardi O, Banfi S, Borsani G, Jonveaux P, Philippe C, Zuccotti M, Ballabio A, Toniolo D
Title
A human homologue of the Drosophila melanogaster diaphanous gene is disrupted in a patient with premature ovarian failure: evidence for conserved function in oogenesis and implications for human sterility.
Di Pasquale E, Rossetti R, Marozzi A, Bodega B, Borgato S, Cavallo L, Einaudi S, Radetti G, Russo G, Sacco M, Wasniewska M, Cole T, Beck-Peccoz P, Nelson LM, Persani L
Title
Identification of new variants of human BMP15 gene in a large cohort of women with premature ovarian failure.
Lourenco D, Brauner R, Lin L, De Perdigo A, Weryha G, Muresan M, Boudjenah R, Guerra-Junior G, Maciel-Guerra AT, Achermann JC, McElreavey K, Bashamboo A
Title
Mutations in NR5A1 associated with ovarian insufficiency.
Caburet S, Arboleda VA, Llano E, Overbeek PA, Barbero JL, Oka K, Harrison W, Vaiman D, Ben-Neriah Z, Garcia-Tunon I, Fellous M, Pendas AM, Veitia RA, Vilain E
Franca MM, Funari MFA, Nishi MY, Narcizo AM, Domenice S, Costa EMF, Lerario AM, Mendonca BB
Title
Identification of the first homozygous 1-bp deletion in GDF9 gene leading to primary ovarian insufficiency by using targeted massively parallel sequencing.
Zhang D, Liu Y, Zhang Z, Lv P, Liu Y, Li J, Wu Y, Zhang R, Huang Y, Xu G, Qian Y, Qian Y, Chen S, Xu C, Shen J, Zhu L, Chen K, Zhu B, Ye X, Mao Y, Bo X, Zhou C, Wang T, Chen D, Yang W, Tan Y, Song Y, Zhou D, Sheng J, Gao H, Zhu Y, Li M, Wu L, He L, Huang H
Title
Basonuclin 1 deficiency is a cause of primary ovarian insufficiency.
Fan S, Jiao Y, Khan R, Jiang X, Javed AR, Ali A, Zhang H, Zhou J, Naeem M, Murtaza G, Li Y, Yang G, Zaman Q, Zubair M, Guan H, Zhang X, Ma H, Jiang H, Ali H, Dil S, Shah W, Ahmad N, Zhang Y, Shi Q
Title
Homozygous mutations in C14orf39/SIX6OS1 cause non-obstructive azoospermia and premature ovarian insufficiency in humans.
Wu H, Zhang X, Hua R, Li Y, Cheng L, Li K, Liu Y, Gao Y, Shen Q, Wang G, Lv M, Xu Y, He X, Cao Y, Liu M
Title
Homozygous missense mutation in CCDC155 disrupts the transmembrane distribution of CCDC155 and SUN1, resulting in non-obstructive azoospermia and premature ovarian insufficiency in humans.
Caburet S, Todeschini AL, Petrillo C, Martini E, Farran ND, Legois B, Livera G, Younis JS, Shalev S, Veitia RA
Title
A truncating MEIOB mutation responsible for familial primary ovarian insufficiency abolishes its interaction with its partner SPATA22 and their recruitment to DNA double-strand breaks.
Tang S, Guo T, Song C, Wang L, Zhang J, Rajkovic A, Lin X, Chen S, Liu Y, Tian W, Wu B, Wang S, Wang W, Lai Y, Wang A, Xu S, Jin L, Ke H, Zhao S, Li Y, Qin Y, Zhang F, Chen ZJ
Title
MGA loss-of-function variants cause premature ovarian insufficiency.
Fragile X tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder affecting carriers of premutation CGG repeat expansions (range: 55-200) in the fragile X mental retardation 1 (FMR1) gene. Common manifestations of FXTAS are progressive intention tremor, cerebellar gait ataxia, parkinsonism, working memory impairment, and frontal executive dysfunction. FXTAS occurs predominantly in men over age 50 years.
Category
Chromosomal abnormality
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Chromosomal anomalies, excluding gene mutations
Sex chromosome anomalies
LD55 Fragile X chromosome
H01731 Fragile X tremor/ataxia syndrome
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06541 Cytoskeleton in neurons
H01731 Fragile X tremor/ataxia syndrome
See also H00465 Fragile X syndrome (FXS).
(FXR) Full mutation expansions (>200 CGG repeats)
(FXTAS) Smaller expansions in the premutation range (55-200 CGG repeats)
