Cytogenetically visible inversions are formed by multiple molecular mechanisms.


:Cytogenetically detected inversions are generally assumed to be copy number and phenotypically neutral events. While nonallelic homologous recombination is thought to play a major role, recent data suggest the involvement of other molecular mechanisms in inversion formation. Using a combination of short-read whole-genome sequencing (WGS), 10X Genomics Chromium WGS, droplet digital polymerase chain reaction and array comparative genomic hybridization we investigated the genomic structure of 18 large unique cytogenetically detected chromosomal inversions and achieved nucleotide resolution of at least one chromosomal inversion junction for 13/18 (72%). Surprisingly, we observed that seemingly copy number neutral inversions can be accompanied by a copy-number gain of up to 350 kb and local genomic complexities (3/18, 17%). In the resolved inversions, the mutational signatures are consistent with nonhomologous end-joining (8/13, 62%) or microhomology-mediated break-induced replication (5/13, 38%). Our study indicates that short-read 30x coverage WGS can detect a substantial fraction of chromosomal inversions. Moreover, replication-based mechanisms are responsible for approximately 38% of those events leading to a significant proportion of inversions that are actually accompanied by additional copy-number variation potentially contributing to the overall phenotypic presentation of those patients.


Hum Mutat


Human mutation


Pettersson M,Grochowski CM,Wincent J,Eisfeldt J,Breman AM,Cheung SW,Krepischi ACV,Rosenberg C,Lupski JR,Ottosson J,Lovmar L,Gacic J,Lundberg ES,Nilsson D,Carvalho CMB,Lindstrand A




Has Abstract


2020-11-01 00:00:00












  • Detection of thirty novel FBN1 mutations in patients with Marfan syndrome or a related fibrillinopathy.

    abstract::Marfan syndrome (MFS) is a disorder of the extracellular matrix caused by mutations in the gene encoding fibrillin-1 (FBN1). Recent studies have illustrated the variability in disease severity and clinical manifestations of MFS. Useful genotype-phenotype correlations have been slow to emerge. We screened 57 unrelated ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Biggin A,Holman K,Brett M,Bennetts B,Adès L

    更新日期:2004-01-01 00:00:00

  • Mandibular-pelvic-patellar syndrome is a novel PITX1-related disorder due to alteration of PITX1 transactivation ability.

    abstract::PITX1 is a homeobox transcription factor essential for hindlimb morphogenesis. Two PITX1-related human disorders have been reported to date: PITX1 ectopic expression causes Liebenberg syndrome, characterized by malformation of upper limbs showing a "lower limb" appearance; PITX1 deletions or missense variation cause a...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Morel G,Duhamel C,Boussion S,Frénois F,Lesca G,Chatron N,Labalme A,Sanlaville D,Edery P,Thevenon J,Faivre L,Fassier A,Prodhomme O,Escande F,Manouvrier S,Petit F,Geneviève D,Rossi M

    更新日期:2020-09-01 00:00:00

  • Mutations in the genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) in diabetes mellitus and hyperinsulinism.

    abstract::The beta-cell ATP-sensitive potassium channel is a key component of stimulus-secretion coupling in the pancreatic beta-cell. The channel couples metabolism to membrane electrical events, bringing about insulin secretion. Given the critical role of this channel in glucose homeostasis, it is not surprising that mutation...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Gloyn AL,Siddiqui J,Ellard S

    更新日期:2006-03-01 00:00:00

  • Genetic findings in congenital bilateral aplasia of vas deferens patients and identification of six novel mutatations. Mutations in brief no. 138. Online.

    abstract::Congential bilateral aplasia of vas deferens (CBAVD), a form of male sterility, has been suggested to represent a "genital" form of cystic fibrosis (CF), as mutations in the CFTR gene have been identified in most patients with this condition. Interestingly, the 5T allele in intron 8 appeared to be the most frequent mu...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: de Meeus A,Guittard C,Desgeorges M,Carles S,Demaille J,Claustres M

    更新日期:1998-01-01 00:00:00

  • Two novel mutations consisting in minor gene rearrangements in the human low density lipoprotein receptor gene in Italian patients affected by familial hypercholesterolemia. Mutations in brief no. 194. Online.

    abstract::Mutations in the low density lipoprotein (LDL)-receptor gene cause familial hypercholesterolemia (FH), an autosomal dominant disease associated to an increased risk of premature atherosclerosis. We describe two novel mutations found in Italian families and consisting in minor gene rearrangements. The first one (FH-Pis...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Motti C,Bertolini S,Rampa P,Trovatello G,Liberatoscioli L,Calandra S,Federici G,Cortese C

    更新日期:1998-01-01 00:00:00

  • Identification of novel mutations in the SLC25A15 gene in hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome: a clinical, molecular, and functional study.

    abstract::Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is an autosomal recessive disorder of the urea cycle. With the exception of the French-Canadian founder effect, no common mutation has been detected in other populations. In this study, we collected 16 additional HHH cases and expanded the spectrum of S...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Tessa A,Fiermonte G,Dionisi-Vici C,Paradies E,Baumgartner MR,Chien YH,Loguercio C,de Baulny HO,Nassogne MC,Schiff M,Deodato F,Parenti G,Rutledge SL,Vilaseca MA,Melone MA,Scarano G,Aldamiz-Echevarría L,Besley G,Walter

    更新日期:2009-05-01 00:00:00

  • Nonsense-mediated and nonstop decay of ribosomal protein S19 mRNA in Diamond-Blackfan anemia.

    abstract::Mutations in the ribosomal protein (RP)S19 gene have been found in about 25% of the cases of Diamond-Blackfan anemia (DBA), a rare congenital hypoplastic anemia that includes variable physical malformations. Various mutations have been identified in the RPS19 gene, but no investigations regarding the effect of these a...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Chatr-Aryamontri A,Angelini M,Garelli E,Tchernia G,Ramenghi U,Dianzani I,Loreni F

    更新日期:2004-12-01 00:00:00

  • A new PCR assay useful for screening of FRAXE/FMR2 mental impairment among males.

    abstract::FRAXE (FMR2) is a fragile site associated with mental impairment located in Xq28, 600 kb distal to FRAXA (FMR1), the fragile X syndrome fragile site. The FRAXE mutation is an expansion of a CCG repeat that results in methylation of a nearby CpG island. FRAXE alleles could be divided into four categories: normal (6-30 ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Santos CB,Costa Lima MA,Pimentel MM

    更新日期:2001-08-01 00:00:00

  • Mutation rate of MAP2K4/MKK4 in breast carcinoma.

    abstract::The stress-activated protein kinase (SAPK) pathways represent phosphorylation cascades that convey pro-apoptotic signals. The relevant inputs include Ras proteins as well as exposure of cells to ultraviolet light, tumor-necrosis factor, and other stress-related inputs. The mitogen-activated protein kinase kinase (MAPK...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Su GH,Song JJ,Repasky EA,Schutte M,Kern SE

    更新日期:2002-01-01 00:00:00

  • Coincidence of two novel arylsulfatase A alleles and mutation 459+1G>A within a family with metachromatic leukodystrophy: molecular basis of phenotypic heterogeneity.

    abstract::In a family with three siblings, one developed classical late infantile metachromatic leukodystrophy (MLD), fatal at age 5 years, with deficient arylsulfatase A (ARSA) activity and increased galactosylsulfatide (GS) excretion. The two other siblings, apparently healthy at 12(1/2) and 15 years, respectively, and their ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Berger J,Gmach M,Mayr U,Molzer B,Bernheimer H

    更新日期:1999-01-01 00:00:00

  • Mosaicism for dominant collagen 6 mutations as a cause for intrafamilial phenotypic variability.

    abstract::Collagen 6-related dystrophies and myopathies (COL6-RD) are a group of disorders that form a wide phenotypic spectrum, ranging from severe Ullrich congenital muscular dystrophy, intermediate phenotypes, to the milder Bethlem myopathy. Both inter- and intrafamilial variable expressivity are commonly observed. We presen...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Donkervoort S,Hu Y,Stojkovic T,Voermans NC,Foley AR,Leach ME,Dastgir J,Bolduc V,Cullup T,de Becdelièvre A,Yang L,Su H,Meilleur K,Schindler AB,Kamsteeg EJ,Richard P,Butterfield RJ,Winder TL,Crawford TO,Weiss RB,Mun

    更新日期:2015-01-01 00:00:00

  • Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy.

    abstract::Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated with general skeletal muscle weakness, type I fiber predominance and atrophy, and abnormally centralized nuclei. Autosomal dominant CNM is due to mutations in the large GTPase dynamin 2 (DNM2), a mechanochemical enzyme regulating cytoskele...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Böhm J,Biancalana V,Dechene ET,Bitoun M,Pierson CR,Schaefer E,Karasoy H,Dempsey MA,Klein F,Dondaine N,Kretz C,Haumesser N,Poirson C,Toussaint A,Greenleaf RS,Barger MA,Mahoney LJ,Kang PB,Zanoteli E,Vissing J,Wittin

    更新日期:2012-06-01 00:00:00

  • Expanding the genetic and phenotypic relevance of KCNB1 variants in developmental and epileptic encephalopathies: 27 new patients and overview of the literature.

    abstract::Developmental and epileptic encephalopathies (DEE) refer to a heterogeneous group of devastating neurodevelopmental disorders. Variants in KCNB1 have been recently reported in patients with early-onset DEE. KCNB1 encodes the α subunit of the delayed rectifier voltage-dependent potassium channel Kv 2.1. We review the 3...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Bar C,Barcia G,Jennesson M,Le Guyader G,Schneider A,Mignot C,Lesca G,Breuillard D,Montomoli M,Keren B,Doummar D,Billette de Villemeur T,Afenjar A,Marey I,Gerard M,Isnard H,Poisson A,Dupont S,Berquin P,Meyer P,Gene

    更新日期:2020-01-01 00:00:00

  • Mucopolysaccharidosis type VI (MPS VI) and molecular analysis: Review and classification of published variants in the ARSB gene.

    abstract::Maroteaux-Lamy syndrome (MPS VI) is an autosomal recessive lysosomal storage disorder caused by pathogenic ARSB gene variants, commonly diagnosed through clinical findings and deficiency of the arylsulfatase B (ASB) enzyme. Detection of ARSB pathogenic variants can independently confirm diagnosis and render genetic co...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Tomanin R,Karageorgos L,Zanetti A,Al-Sayed M,Bailey M,Miller N,Sakuraba H,Hopwood JJ

    更新日期:2018-12-01 00:00:00

  • Rapid classification of phenylketonuria genotypes by analysis of heteroduplexes generated by PCR-amplifiable synthetic DNA.

    abstract::We describe a rapid and simple method for phenylketonuria genotyping which identifies five point mutations within exon 12 of the human phenylalanine hydroxylase gene. The method involves PCR amplification of the target exon and hybridization with a PCR-amplifiable synthetic DNA (universal heteroduplex generator, UHG)....

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Wood N,Tyfield L,Bidwell J

    更新日期:1993-01-01 00:00:00

  • Three-Dimensional Model of Human Nicotinamide Nucleotide Transhydrogenase (NNT) and Sequence-Structure Analysis of its Disease-Causing Variations.

    abstract::Defective mitochondrial proteins are emerging as major contributors to human disease. Nicotinamide nucleotide transhydrogenase (NNT), a widely expressed mitochondrial protein, has a crucial role in the defence against oxidative stress. NNT variations have recently been reported in patients with familial glucocorticoid...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Metherell LA,Guerra-Assunção JA,Sternberg MJ,David A

    更新日期:2016-10-01 00:00:00

  • Mutations and polymorphisms in the human methyl CpG-binding protein MECP2.

    abstract::Rett syndrome (RTT or RS) is a neurodevelopmental disorder and one of the most frequent genetic diseases in girls. Mutations of the MECP2 gene have been found in a variety of different RTT phenotypes. The MECP2 gene (Xq28) has been described in 1992. Up to now, 218 different mutations have been reported in a total gro...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Miltenberger-Miltenyi G,Laccone F

    更新日期:2003-08-01 00:00:00

  • Broad phenotypic variability in a single pedigree with a novel 1410delC mutation in the PST domain of the PAX6 gene.

    abstract::The PAX6 mutation present in an individual with aniridia was determined and phenotypic features of immediate relatives carrying the same mutation investigated. Mutation analysis revealed a novel single base deletion 1410delC in the PAX6 gene in ten affected individuals. Clinical features ranged from total aniridia to ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Sale MM,Craig JE,Charlesworth JC,FitzGerald LM,Hanson IM,Dickinson JL,Matthews SJ,Heyningen Vv Vv,Fingert JH,Mackey DA

    更新日期:2002-10-01 00:00:00

  • Mutant NR5A1/SF-1 in patients with disorders of sex development shows defective activation of the SOX9 TESCO enhancer.

    abstract::Nuclear receptor subfamily 5 group A member 1/Steroidogenic factor 1 (NR5A1; SF-1; Ad4BP) mutations cause 46,XY disorders of sex development (DSD), with phenotypes ranging from developmentally mild (e.g., hypospadias) to severe (e.g., complete gonadal dysgenesis). The molecular mechanism underlying this spectrum is un...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Sreenivasan R,Ludbrook L,Fisher B,Declosmenil F,Knower KC,Croft B,Bird AD,Ryan J,Bashamboo A,Sinclair AH,Koopman P,McElreavey K,Poulat F,Harley VR

    更新日期:2018-12-01 00:00:00

  • Detection of genomic copy number changes in patients with idiopathic mental retardation by high-resolution X-array-CGH: important role for increased gene dosage of XLMR genes.

    abstract::A tiling X-chromosome-specific genomic array with a theoretical resolution of 80 kb was developed to screen patients with idiopathic mental retardation (MR) for submicroscopic copy number differences. Four patients with aberrations previously detected at lower resolution were first analyzed. This facilitated delineati...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Froyen G,Van Esch H,Bauters M,Hollanders K,Frints SG,Vermeesch JR,Devriendt K,Fryns JP,Marynen P

    更新日期:2007-10-01 00:00:00

  • MEFV mutations in Behçet's disease.

    abstract::Familial Mediterranean fever (FMF) and Behçet's disease (BD), both inflammatory diseases, are highly prevalent in the Middle Eastern and Mediterranean populations. FMF is a Mendelian autosomic recessive disease linked to MEFV, a gene of unknown function. BD in contrast is a polyfactorial disease associated with the ma...

    journal_title:Human mutation

    pub_type: 杂志文章,多中心研究


    authors: Touitou I,Magne X,Molinari N,Navarro A,Quellec AL,Picco P,Seri M,Ozen S,Bakkaloglu A,Karaduman A,Garnier JM,Demaille J,Koné-Paut I

    更新日期:2000-09-01 00:00:00

  • Novel NOBOX loss-of-function mutations account for 6.2% of cases in a large primary ovarian insufficiency cohort.

    abstract::Primary ovarian insufficiency (POI) is a disorder associated with female infertility, which affects approximately 1% of women under 40 years of age. A genetic component has been suggested as one possible cause of the majority of cases of nonsyndromic forms. Newborn Ovary Homeobox (NOBOX) is an ovary-specific gene, pla...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Bouilly J,Bachelot A,Broutin I,Touraine P,Binart N

    更新日期:2011-10-01 00:00:00

  • Rapid detection of the R408W and I65T mutations in phenylketonuria by glycosylase mediated polymorphism detection.

    abstract::Mutation detection methods based upon chemical or enzymatic cleavage of DNA offer excellent detection efficiencies coupled with high throughput and low unit cost. We describe the application of the novel technique of Glycosylase Mediated Polymorphism Detection (GMPD) to the detection of two of the most common mutation...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: O'Donnell KA,Tighe O,O'Neill C,Naughten E,Mayne PD,McCarthy TV,Vaughan P,Croke DT

    更新日期:2001-05-01 00:00:00

  • Targeted resequencing reveals genetic risks in patients with sporadic idiopathic pulmonary fibrosis.

    abstract::Idiopathic pulmonary fibrosis (IPF) is a genetic heterogeneous disease with high mortality and poor prognosis. However, a large fraction of genetic cause remains unexplained, especially in sporadic IPF (∼80% IPF). By systemically reviewing related literature and potential pathogenic pathways, 92 potentially IPF-relate...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Deng Y,Li Z,Liu J,Wang Z,Cao Y,Mou Y,Fu B,Mo B,Wei J,Cheng Z,Luo L,Li J,Shu Y,Wang X,Luo G,Yang S,Wang Y,Zhu J,Yang J,Wu M,Xu X,Ge R,Chen X,Peng Q,Wei G,Li Y,Yang H,Fang S,Zhang X,Xiong W

    更新日期:2018-09-01 00:00:00

  • Identification of a 5' splice site mutation in the RPGR gene in a family with X-linked retinitis pigmentosa (RP3).

    abstract::We have identified a novel RPGR gene mutation in a large Dutch family with X-linked retinitis pigmentosa (RP3). In affected members, a G-->T transversion was found at position +1 of the 5' splice site of intron 5 of the RPGR (retinitis pigmentosa GTPase regulator) gene. Analysis of this mutation at the RNA level showe...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Dry KL,Manson FD,Lennon A,Bergen AA,Van Dorp DB,Wright AF

    更新日期:1999-01-01 00:00:00

  • Predicting functional variants in enhancer and promoter elements using RegulomeDB.

    abstract::Here we present a computational model, Score of Unified Regulatory Features (SURF), that predicts functional variants in enhancer and promoter elements. SURF is trained on data from massively parallel reporter assays and predicts the effect of variants on reporter expression levels. It achieved the top performance in ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Dong S,Boyle AP

    更新日期:2019-09-01 00:00:00

  • Identification and characterization of a novel RPGR isoform in human retina.

    abstract::Retinitis pigmentosa (RP) constitutes a major cause of blindness and the Retinitis Pigmentosa GTPase Regulator (RPGR) gene accounts for up to 80% of all X-linked RP cases. A novel isoform of RPGR, expressed in the human retina, was identified and characterized. It truncates the Regulator of Chromosome Condensation 1 (...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Neidhardt J,Glaus E,Barthelmes D,Zeitz C,Fleischhauer J,Berger W

    更新日期:2007-08-01 00:00:00

  • Alternative splicing of in-frame exon associated with premature termination codons: implications for readthrough therapies.

    abstract::The correction of premature termination codons (PTCs) by agents that promote readthrough represents a promising emerging tool for the treatment of many genetic diseases. The efficiency of the treatment, however, varies depending on the stop codon itself and the amount of correctible transcripts related to the efficien...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Hinzpeter A,Aissat A,de Becdelièvre A,Bieth E,Sondo E,Martin N,Costes B,Costa C,Goossens M,Galietta LJ,Girodon E,Fanen P

    更新日期:2013-02-01 00:00:00

  • Screening for new mutations in the LDL receptor gene in seven French familial hypercholesterolemia families by the single strand conformation polymorphism method.

    abstract::To investigate the molecular basis of familial hypercholesterolemia (FH) in France, we applied the single strand conformation polymorphism (SSCP) method to the promoter region and the 18 exons of the low density lipoprotein receptor (LDLR) gene. Seven probands, 4 heterozygotes, 2 compound heterozygotes, and 1 homozygo...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Loux N,Saint-Jore B,Collod G,Dairou F,Benlian P,Truffert J,Dastugue B,Douste-Blazy P,de Gennes JL,Junien C

    更新日期:1992-01-01 00:00:00

  • Conservation of the RB1 gene in human and primates.

    abstract::Mutations in the RB1 gene are associated with retinoblastoma, which has served as an important model for understanding hereditary predisposition to cancer. Despite the great scrutiny that RB1 has enjoyed as the prototypical tumor suppressor gene, it has never been the object of a comprehensive survey of sequence varia...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Sivakumaran TA,Shen P,Wall DP,Do BH,Kucheria K,Oefner PJ

    更新日期:2005-04-01 00:00:00