ライフサイエンスコーパス: monogenic

1 gies has revealed that genomic disorders and monogenic aetiologies contribute meaningfully to seeming

2 the enteric nervous system, as well as with monogenic and chromosomal syndromes.

3 ial to treat an extensive range of incurable monogenic and complex diseases.

4 red allergic diseases exist on a spectrum of monogenic and complex genetic etiologies that are impact

5 erlying CHD and discuss data supporting both monogenic and complex genetic mechanisms underlying CHD.

6 s, following a quasi-Mendelian model linking monogenic and complex inheritance.

7 PMS is a relatively common monogenic and highly penetrant cause of autism spectrum

8 The monogenic and monoallelic expression of only one out of

9 tructure and/or function, and encompass both monogenic and polygenic aetiologies.

10 We confirm genetic overlap between human monogenic and polygenic anthropometric traits and find s

11 these RIPK1 inhibitors for the treatment of monogenic and polygenic autoimmune, inflammatory, neurod

12 This study evaluated the effect of monogenic and polygenic causes of FH on premature (age <

13 Autoinflammatory diseases are monogenic and polygenic disorders due to dysregulation o

14 Both monogenic and polygenic factors contribute to AF risk in

15 Genetic approaches, studying both monogenic and polygenic factors in nephrolithiasis, have

16 d extra-renal manifestations, revealing both monogenic and polygenic mechanisms.

17 studies have explored the interplay between monogenic and polygenic risk.

18 se, why cellular pathways can be modified in monogenic and polygenic traits, and how the environment

19 dels and characterized and compared digenic, monogenic, and wild-type phenotypes.

20 ease networks and pathological mechanisms of monogenic as opposed to complex retinopathies, using AMD

21 zing registries and biobanks to reveal other monogenic atypical forms of diabetes is an important app

22 iency of the Shank3 gene (a highly penetrant monogenic autism risk factor), which exhibits prominent

23 Diagnosing monogenic autoimmunity is crucial for patients' prognosi

24 from genome instability in a mouse model of monogenic autoinflammation, after exogenous DNA damage a

25 tion-associated alterations in patients with monogenic autoinflammatory disease and opens up possibil

26 ed disease and introduce major categories of monogenic autoinflammatory disorders recognized to date,

27 familial Mediterranean fever, 2 archetypical monogenic autoinflammatory syndromes.

28 use of a few animal models with restrictive monogenic backgrounds that may be more resistant to kidn

29 The causes are heterogeneous, with a monogenic basis identified in ~25% of patients.

30 mary HLH occurs early in life as a result of monogenic biallelic mutations affecting lymphocyte cytot

31 Monogenic blood pressure syndromes predominantly involve

32 from GWAS are mapped to known genes causing monogenic blood pressure syndromes.

33 esent the genomes of Chrysomya rufifacies, a monogenic blow fly (females produce female or male offsp

34 t most inheritable cardiac disorders are not monogenic but, rather, have a complex genetic basis wher

35 se findings suggest that PBX1 is involved in monogenic CAKUT in humans and call into question the rol

36 l proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide asso

37 this study was to estimate the prevalence of monogenic cardiovascular diseases (MCVDs) and potentiall

38 2 (FOXP2) gene in humans are the first known monogenic cause of a speech and language disorder.

39 Fragile X syndrome (FXS) is the leading monogenic cause of autism spectrum disorders (ASD).

40 oding gene has been strongly implicated as a monogenic cause of autism, and Shank3 mutant mice show r

41 Fragile X syndrome, the most common known monogenic cause of autism, results from the loss of FMR1

42 ous CTLA-4 deficiency has been reported as a monogenic cause of common variable immune deficiency wit

43 EMA may be an effective way of elucidating a monogenic cause of death and bringing clarity to otherwi

44 The study was undertaken to identify a monogenic cause of early onset, generalized dystonia.

45 ic kidney disease (ADPKD) is the most common monogenic cause of end-stage renal failure in humans and

46 A monogenic cause of FH was associated with significantly

47 essive neuromuscular disease, is the leading monogenic cause of infant mortality.

48 mechanisms that contribute to this proposed monogenic cause of intellectual disability and epilepsy

49 gnificant de novo enrichment P = 0.003) as a monogenic cause of mild and non-specific neurodevelopmen

50 tal LUTO caused by anatomical blockage has a monogenic cause.

51 equencing, performed to identify a potential monogenic cause.

52 Though only seven monogenic causes (19%) were identified in more than one

53 Few monogenic causes for severe manifestations of common all

54 We aimed to elucidate the monogenic causes for the major clinical categories of dy

55 Monogenic causes of CAKUT in humans and mice have been i

56 Despite the discovery of dozens of monogenic causes of CAKUT, most pathogenic pathways rema

57 The analyses captured five established monogenic causes of CKD: variants in PKD1, PKD2, and COL

58 of genes have so far been identified as the monogenic causes of disease(2-7).

59 However, despite many known monogenic causes of FSGS, single gene defects explain on

60 Although several monogenic causes of functional obstruction have been def

61 We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS

62 The discovery of >60 monogenic causes of nephrotic syndrome (NS) has revealed

63 ny genetic mutations have been identified as monogenic causes of nephrotic syndrome (NS), but importa

64 t, we screened Drosophila orthologs of human monogenic causes of nephrotic syndrome and observed cons

65 ns in about 50 genes have been identified as monogenic causes of nephrotic syndrome, a frequent cause

66 stamine dysregulation.SIGNIFICANCE STATEMENT Monogenic causes of neurologic disorders, although rare,

67 Novel mutations in TBC1D8B are monogenic causes of SRNS.

68 sed whole-exome sequencing to identify novel monogenic causes of steroid-resistant nephrotic syndrome

69 es of embryo loss and variable penetrance of monogenic CHD, and raises the possibility that cases of

70 ntained or perturbed in different hereditary monogenic conditions and in acquired conditions that mim

71 Singleton WES in children with suspected monogenic conditions has high diagnostic yield, and cost

72 ically ill pediatric patients with suspected monogenic conditions in the Australian public health car

73 ically ill pediatric patients with suspected monogenic conditions treated at 12 Australian hospitals

74 than 4,500 genes reportedly associated with monogenic conditions, as well as pharmacogenomic (PGx) m

75 ded rapidly to include more than 40 distinct monogenic conditions.

76 e changes in human NR genes associated with "monogenic" conditions, including a discussion of the str

77 er-represented among cell-essential genes in monogenic CRISPR-based loss of function screens.

78 Of the 17 patients with monogenic Crohn's disease, 35% had abdominal pain, 24% h

79 able genes robustly associated with dominant monogenic DCM.

80 Identifying gene variants causing monogenic diabetes (MD) increases understanding of disea

81 of pathways on type 2 diabetes (for example, monogenic diabetes and beta cells).

82 Identifying genes that result in monogenic diabetes can provide insights that can build a

83 diabetes those who carry mutations in known monogenic diabetes genes is the first step to then allow

84 Monogenic diabetes genes were screened for the entire co

85 abetes of adulthood carry mutations in known monogenic diabetes genes.

86 Gene discovery efforts in monogenic diabetes have identified 36 genes so far.

87 Finding new causes of monogenic diabetes helps understand glycaemic regulation

88 any with HLA+ diabetes risk alleles also had monogenic diabetes variants, indicating the importance o

89 ysis revealed that 280 Medalists (27.5%) had monogenic diabetes variants; in 80 (7.9%) of these Medal

90 Human monogenic diabetes, caused by mutations in genes involve

91 used by a subset of GCK mutations that cause monogenic diabetes, electrical coupling exacerbates [Ca(

92 cells to understand the most common form of monogenic diabetes, MODY3, caused by mutations in the tr

93 ntification of seven novel genetic causes of monogenic diabetes, six by exome sequencing and one by g

94 iant associated with the most common form of monogenic diabetes, we found that HNF1A dysfunction lead

95 evaluated in a national reference center for monogenic diabetes.

96 imulating GK gene (GCK) mutations that cause monogenic diabetes.

97 CM10 has not been previously associated with monogenic disease and plays a critical role in the activ

98 Cystic Fibrosis (CF) is a monogenic disease caused by mutations in the cystic fibr

99 Exome analysis of patients with a likely monogenic disease does not identify a causal variant in

100 We aimed to determine the prevalence of monogenic disease in a cohort of pediatric patients with

101 Monogenic disease risk and carrier status were reported

102 Only two participants had no monogenic disease risk or carrier status identified.

103 Hemophilia A is a monogenic disease with a blood clotting factor VIII (FVI

104 ed and a further 52 genes are known to cause monogenic disease, often presenting in infancy.

105 re a pre-dominant cause of sporadic dominant monogenic diseases and play a significant role in the ge

106 While most monogenic diseases are caused by loss or reduction of pr

107 Monogenic diseases are individually rare but collectivel

108 Monogenic diseases due to hepatic enzymes deficiency res

109 Thousands of monogenic diseases have yielded definitive genomic diagn

110 (LT-HSCs) could be an effective therapy for monogenic diseases of the blood and immune system.

111 Monogenic diseases provide favorable opportunities to el

112 imary atopic disorders describes a series of monogenic diseases that have allergy- or atopic effector

113 beta-Thalassaemia is one of the most common monogenic diseases with no effective cure in the majorit

114 DT) and sickle cell disease (SCD) are severe monogenic diseases with severe and potentially life-thre

115 and sickle-cell disease, are the most common monogenic diseases worldwide.

116 We propose that the study of monogenic diseases, and in particular STAT mutations, ma

117 requently uncovered cell-level phenotypes in monogenic diseases, but translation to tissue-level and

118 the detection of a wide spectrum of dominant monogenic diseases, complementing current screening for

119 iagnostic, carrier and predictive testing in monogenic diseases.

120 le cell disease (SCD) are the most prevalent monogenic diseases.

121 nel of causative genes for frequent dominant monogenic diseases.

122 or are in genes known to cause two specific monogenic diseases: maturity-onset diabetes of the young

123 Duchenne muscular dystrophy (DMD) is a monogenic disorder and a candidate for therapeutic genom

124 The monogenic disorder called hereditary alpha-tryptasemia,

125 Cystic fibrosis (CF) is a monogenic disorder caused by mutations in the Cystic Fib

126 Duchenne muscular dystrophy (DMD), a lethal monogenic disorder caused by the loss of the large cytos

127 Alstrom syndrome (AS) is a rare monogenic disorder characterized by progressive multi-or

128 ickle cell disease is the most common severe monogenic disorder in humans.

129 A rare, monogenic disorder in which children with mutations in m

130 The most common aaRS-associated monogenic disorder is the incurable neurodegenerative di

131 Sickle cell disease (SCD) is a monogenic disorder that affects millions worldwide.

132 ren older than 2 years suspected of having a monogenic disorder were prospectively recruited from May

133 Huntington's disease (HD) is a monogenic disorder with 100% penetrance.

134 ften-diverse phenotypes of an extremely rare monogenic disorder.

135 tosus, rheumatoid arthritis, and devastating monogenic disorders (interferonopathies) characterized b

136 uch as pathogenic variants leading mostly to monogenic disorders and pharmacogenomics biomarkers.

137 niques have led to the identification of new monogenic disorders and their corresponding signaling pa

138 A number of monogenic disorders are associated with VEOIBD including

139 Monogenic disorders are caused by rare genetic variation

140 However, screening for many dominant monogenic disorders associated with de novo mutations is

141 could be targeted to treat striatal-related monogenic disorders associated with the mTOR signaling p

142 cystic kidney disease, accounting for ~5% of monogenic disorders causing chronic kidney disease.

143 Type I interferonopathies are monogenic disorders characterized by enhanced type I int

144 ory was first reported in 1999 as a group of monogenic disorders characterized by recurrent episodes

145 al storage diseases (LSDs) are a group of 70 monogenic disorders characterized by the lysosomal accum

146 ix of seven (86%) de novo variant associated monogenic disorders for which epidemiological estimates

147 ecular basis of the incomplete penetrance of monogenic disorders is unclear.

148 Some monogenic disorders may therefore actually be digenic.

149 Studies of monogenic disorders might provide critical insights into

150 Monogenic disorders occur at a high frequency in human p

151 utations in AKT2 are an established cause of monogenic disorders of glucose metabolism.

152 These include monogenic disorders of key proteins involved in the auto

153 erged as an effective treatment modality for monogenic disorders of the blood system such as primary

154 peats have been associated with more than 40 monogenic disorders(1).

155 epeat expansions are responsible for over 40 monogenic disorders, and undoubtedly more pathogenic rep

156 (ADPKD) is one of the most common inherited monogenic disorders, characterized by a progressive decl

157 he emergence of a new class of therapies for monogenic disorders, which had hitherto been considered

158 (19%) of 728 families, involving 78 distinct monogenic disorders.

159 ng its therapeutic potential for early-onset monogenic disorders.

160 5 patients (9.3%), encompassing 66 different monogenic disorders.

161 rogeneous phenotypes that arise in many rare monogenic disorders.

162 78 probands (56%), encompassing 152 distinct monogenic disorders.

163 the discovery of genetic lesions underlying monogenic disorders.

164 lopmental disorders as well as 3106 putative monogenic disorders.

165 PubMed for studies on genetically confirmed monogenic dystonia treated with GPi DBS documenting pre-

166 ator A), the product of another gene causing monogenic dystonia.

167 d BFMDS outcomes between DYT-TOR1A and other monogenic dystonias, adjusting for age and disease durat

168 GPi DBS outcomes vary across monogenic dystonias.

169 mpare GPi DBS outcomes among the most common monogenic dystonias.

170 in but progress in genomics has revealed new monogenic entities.

171 Monogenic epilepsies with wide-ranging clinical severity

172 Autoinflammatory disease can result from monogenic errors of immunity.

173 velop from hematopoietic stem cells, and few monogenic errors that specifically interrupt NK cell dev

174 We identified two novel monogenic etiologies, FBXO31 and RHOB, and showed that t

175 While monogenic familial hypercholesterolemia associates with

176 further increased CVD risk in patients with monogenic FH (adjusted hazard ratio: 3.06; 95% confidenc

177 Patients with monogenic FH and superimposed elevated LDL-C polygenic r

178 le-nucleotide variants, for individuals with monogenic FH from the British Columbia FH (n=262); Nutri

179 (CVD) risk associated with polygenic versus monogenic FH is unclear.

180 Even among individuals with monogenic FH, there is substantial interindividual varia

181 LDL-C and risk of ASCVD for individuals with monogenic FH.

182 processes are individually perturbed in one monogenic form of ASD, Ptchd1 deletion.

183 polyendocrine syndrome type 1 (APS1), a rare monogenic form of autoimmunity, presents as widespread a

184 Here, we report on a monogenic form of IR-prone obesity, Alstrom syndrome (AL

185 ted in an mARHL case, as a mouse model for a monogenic form of presbycusis.

186 We found enrichment for genes underlying monogenic forms of bone development diseases, and for th

187 n gene discovery strategies used to identify monogenic forms of diabetes caused by reduced pancreatic

188 s >30 genes, with rare variants resulting in monogenic forms of hypertension or hypotension and >1,47

189 nically diverse phenotypes observed for many monogenic forms of nephropathy.

190 resence of variants in genes associated with monogenic forms of neurological and psychiatric disorder

191 chanisms underlying the pathogenesis of most monogenic forms of NS, and to efficiently generate perso

192 This contrasts with other monogenic forms of obesity characterized by excessive hu

193 Monogenic forms of obesity have been identified in <=10%

194 tations in MC4R, is the most common cause of monogenic forms of obesity.

195 also, ultrarare variants likely resulting in monogenic forms, thereby paving the way for treatment wi

196 entified 40 rare variants associated with 21 monogenic genes among 31 of the 1005 children with IBD (

197 and showed enrichment of genes implicated in monogenic glomerular diseases in podocytes.

198 d variants overlap genes that are mutated in monogenic growth disorders and highlight new biological

199 Here we describe individuals with monogenic heterozygous microdeletions in ANKS1B, a predi

200 he magnitude of the selective advantage of a monogenic heterozygous variant in the presence of a homo

201 0 unique mouse gene knockouts identified 140 monogenic 'hits', of which most had no previous immunolo

202 een the only known mechanism responsible for monogenic human disorders of retinal hypovascularization

203 rstood, partly due to a lack of intermediary monogenic human phenotypes.

204 de that DAAM2 variants are a likely cause of monogenic human SRNS due to actin dysregulation in podoc

205 f-function MRAP2 variants are pathogenic for monogenic hyperphagic obesity, hyperglycemia and hyperte

206 tified 87.7% (71/81) of Korean patients with monogenic hypouricemia.

207 Monogenic IBD is rare, but should be considered in analy

208 types associated with a single gene variant (monogenic IBD).

209 Features associated with monogenic IBD, compared to cases of IBD not associated w

210 Here, we demonstrate that patients with monogenic immune dysregulation caused by gain-of-functio

211 to an exponential increase in the number of monogenic immune dysregulatory syndromes diagnosed, wher

212 lar helper T-cell differentiation in defined monogenic immunodeficiencies, we sought to determine the

213 atients may become critically ill because of monogenic inborn errors that disrupt protective immunity

214 with non-conditional, recessive and strictly monogenic inheritance are useful for both hybrid and con

215 storage diseases (LSDs) represent a group of monogenic inherited metabolic disorders characterized by

216 Monogenic interferonopathies are thought to be mediated

217 thy donors, viral infection, and complex and monogenic interferonopathies.

218 Although HD is monogenic, its molecular manifestation appears highly co

219 t, an excessive rate given the prevalence of monogenic kidney and genitourinary disorders.

220 stic kidney disease (ADPKD), the most common monogenic kidney disease.

221 gesting that ADTKD is one of the more common monogenic kidney diseases after autosomal dominant polyc

222 We discuss the advantages of studying rare monogenic kidney diseases, describe effective patient-de

223 Studies suggest that the prevalence of monogenic kidney stone disorders, including renal tubula

224 paralog pairs that have escaped detection by monogenic knockout screens at stringent thresholds.

225 umber of essential genes detected from these monogenic knockout screens is low compared to the number

226 Here we review monogenic lesions of IFN-I signalling pathways and summa

227 GRS, identifying a subset of individuals at monogenic levels of risk: the top 0.25% of metaGRS have

228 ce has facilitated the mapping of a dominant monogenic locus, Prs, conferring Papaya ring-spot virus

229 ue subpopulations enriched in ISGs and/or in monogenic lupus-associated genes classified patients wit

230 he same chromosomal locus and inherited in a monogenic Mendelian fashion.

231 chanisms and blurred the distinction between monogenic (Mendelian) and complex diseases.

232 tory microcircuit in a mouse model of a rare monogenic migraine.

233 alms1 loss-of-function zebrafish mutant as a monogenic model for mechanistic interrogation of T2DM ph

234 Monogenic models allow an opportunity to investigate its

235 to the LPS treatment between the MIA and the monogenic models emerge from differences in the levels o

236 LPS-induced rescue of social deficits in the monogenic models.

237 RNA-seq analysis in the digenic and monogenic mouse models highlighted the ciliary compartme

238 Previous work in monogenic mouse models of absence epilepsy have shown th

239 human diseases, which includes chromosomal, monogenic, multifactorial and mitochondrial diseases.

240 1DZ was sufficient to promote sociability in monogenic mutant mice as well as in MIA offspring.

241 LPS treatment in monogenic mutant mice did not induce amounts of interleu

242 We first identified individuals with a rare, monogenic mutation related to familial hypercholesterole

243 tion of PRS and family history of disease or monogenic mutations and (iv) estimation of the value of

244 g enables simultaneous ascertainment of both monogenic mutations and polygenic score for each individ

245 ults demonstrate the feasibility of inducing monogenic mutations in common marmosets and support the

246 oint to a pathophysiologic sequence by which monogenic mutations in genes that regulate bladder inner

247 Monogenic mutations in the SHANK3 gene, which encodes a

248 ngly clear that nephrotic syndrome caused by monogenic mutations is distinct from immune-driven disea

249 lative prevalence and clinical importance of monogenic mutations related to familial hypercholesterol

250 Due to its monogenic nature, HB is one of the primary targets for g

251 Nevertheless, given their monogenic nature, polyQ disorders are ideal candidates f

252 or passenger mutations, as a result of their monogenic nature.

253 he Arg219His mutation causes the first human monogenic neomorphic and noncanonical inflammasomopathy/

254 d hereditary spastic paraplegia is a complex monogenic neurodegenerative disease that in addition to

255 Spinal Muscular Atrophy (SMA) is a monogenic neurodegenerative disorder and the leading gen

256 lipofuscinoses (NCLs) are a group of fatal, monogenic neurodegenerative disorders with an early onse

257 Neurofibromatosis type 1 (NF1) is a common monogenic neurodevelopmental disorder associated with ph

258 lable for the vast majority of these de novo monogenic neurodevelopmental disorders because of phenot

259 ting that CBLH and DWM are often features of monogenic neurodevelopmental disorders.

260 he underlying mutations responsible for many monogenic neuromuscular diseases.

261 We have shown a relative AT failure in a monogenic obese cohort, a finding supported by observati

262 reat potential as a life-saving treatment of monogenic, oncologic, and infectious diseases.

263 This work demonstrates that monogenic or digenic POLR3A and POLR3C deficiencies conf

264 Species that differ in monogenic or oligogenic traits that affect ecological pe

265 Twenty-three subjects with monogenic or polygenic obesity underwent hyperinsulinemi

266 nomic technologies have revealed a number of monogenic origins and opened the door to therapeutic hop

267 enotype-negative disease eluding the classic monogenic paradigm.

268 dels, with no significant enhancement of the monogenic phenotype until a threshold of reduced express

269 ations in known genes that are implicated in monogenic PID occurred in 10.3% of these patients, and a

270 In our monogenic podocyte ER stress-induced NS/FSGS mouse model

271 In contrast, both proteins were functional monogenic PPCDCs.

272 es, but BACH2 mutations that cause Mendelian monogenic primary immunodeficiency have not previously b

273 PARK2 is the most common gene mutated in monogenic recessive familial cases of Parkinson's diseas

274 ystic kidney disease (ADPKD) is an inherited monogenic renal disease characterised by the accumulatio

275 LNP-delivered mRNA can be used to treat monogenic retinal degenerative disorders of the RPE.

276 (SHANK3) gene represents a highly penetrant, monogenic risk factor for autism spectrum disorder, and

277 Among carriers of a monogenic risk variant, we estimate substantial gradient

278 isk estimation for individuals who inherit a monogenic risk variant.

279 n can predispose to disease both through (i) monogenic risk variants that disrupt a physiologic pathw

280 ing uncertainty over how to treat the quasi "monogenic" role of apolipoprotein E (APOE).

281 The monogenic shell thickness is inversely correlated to mes

282 equency feature based on three components of monogenic signal with different frequency scales.

283 (FOXP2) transcription factor causes a severe monogenic speech and language disorder.

284 Although NF1 is a classic monogenic syndrome, the clinical features of the disorde

285 om the endoplasmic reticulum in several rare monogenic syndromes highly comorbid with autism - fragil

286 signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impa

287 pports evidence for a continuum between rare monogenic syndromic and common polygenic forms of obesit

288 We hypothesized that monogenic syndromic obesity genes are also involved in t

289 humans, DNASE1L3 deficiency causes familial monogenic systemic lupus erythematosus with childhood on

290 imits Vbeta recombination efficiency governs monogenic TCRbeta expression, thereby restraining the ex

291 segregation is extremely important, even for monogenic traits such as shell thickness in oil palm.

292 We mapped several monogenic traits to narrow intervals overlapping with kn

293 es mellitus, and dermatomyositis, as well as monogenic type I interferonopathies.

294 The 14 patients with monogenic ulcerative colitis or IBD-unclassified receive

295 n this study, we have determined the role of monogenic variants across the range of dystonic disorder

296 -and interplay between-novel high-penetrance monogenic variants and common variants (at the PTPN2 and

297 uch as Behcet disease, can be caused by rare monogenic variants in genes of the NF-kappaB pathway.

298 We identified monogenic variants in single case reports and smaller st

299 proaches are used to model the dispersion of monogenic variants through large populations.

300 Of the monogenic variants, 11% (23/211) were present in ExAC, w