Two novel types of contiguous gene deletion of the AVPR2 and ARHGAP4 genes in unrelated Japanese kindreds with nephrogenic diabetes insipidus.


:Study of two families containing individuals with nephrogenic diabetes insipidus (NDI) indicated different types of 21.3 kb and 26.3 kb deletions involving the AVPR2 and ARHGAP4 (RhoGAP C1) genes. In the case of the 21.3 kb deletion, the deletion consensus motif (5'-TGAAGG-3') and polypurine runs, known as the arrest site of polymerase alpha, were detected in the vicinity of the deletion junction. Inverted repeats (7/8 matches), believed to potentiate DNA loop formation, flank the deletion breakpoint. We propose this deletion to be the result of slipped mispairing during DNA replication. In the case of the 26.3 kb deletion, the 12,945 bp inverted region with the 10,003 bp internal deletion was accompanied with the 2,509 bp deletion in the 5'-side and the 13,785 bp deletion in the 3'-side. We defined three deletion junctions in this rearrangement (DJ1, DJ2, and DJ3) from the 5'-side. The surrounding sequence of DJ1 (5'-CCC-3') closely resembled that of DJ3 (5'-AGGG-3') (DJ1; 5'-cCCCgaggg-3', DJ3; 5'-ccccAGGG-3'), and DJ1 was located in the 5'-side of DJ3 without any overlapping in sequence. The immunoglobulin class switch (ICS) motif (5'-TGGGG-3') was found around the complementary sequence of DJ3. There was a 10-base palindrome (5'-aGACAtgtct-3') in the alignment of the DJ2 (5'-GACA-3') region. From these findings, we propose a novel mutation process with the rearrangement probably resulting from stem-loop induced non-homologous recombination in an ICS-like fashion. Both patients, despite lacking ARHGAP4, had no morphological, clinical, or laboratory abnormalities except for those usually found in patients with NDI.


Hum Mutat


Human mutation


Demura M,Takeda Y,Yoneda T,Furukawa K,Usukura M,Itoh Y,Mabuchi H





Has Abstract


2002-01-01 00:00:00














  • Characterization of ATM mutations in 41 Nordic families with ataxia telangiectasia.

    abstract::The Ataxia Telangiectasia Mutation (ATM) gene is mutated in the rare recessive syndrome Ataxia Telangiectasia (AT), which is characterized by cerebellar degeneration, immunodeficiency, and cancer predisposition. In this study, 41 AT families from Denmark, Finland, Norway, and Sweden were screened for ATM mutations. Th...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Laake K,Jansen L,Hahnemann JM,Brondum-Nielsen K,Lönnqvist T,Kääriäinen H,Sankila R,Lähdesmäki A,Hammarström L,Yuen J,Tretli S,Heiberg A,Olsen JH,Tucker M,Kleinerman R,Børresen-Dale AL

    更新日期:2000-09-01 00:00:00

  • MSeqDR: A Centralized Knowledge Repository and Bioinformatics Web Resource to Facilitate Genomic Investigations in Mitochondrial Disease.

    abstract::MSeqDR is the Mitochondrial Disease Sequence Data Resource, a centralized and comprehensive genome and phenome bioinformatics resource built by the mitochondrial disease community to facilitate clinical diagnosis and research investigations of individual patient phenotypes, genomes, genes, and variants. A central Web ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Shen L,Diroma MA,Gonzalez M,Navarro-Gomez D,Leipzig J,Lott MT,van Oven M,Wallace DC,Muraresku CC,Zolkipli-Cunningham Z,Chinnery PF,Attimonelli M,Zuchner S,Falk MJ,Gai X

    更新日期:2016-06-01 00:00:00

  • A pharmacogenetic approach to identify mutant forms of α-galactosidase A that respond to a pharmacological chaperone for Fabry disease.

    abstract::Fabry disease is caused by mutations in the gene (GLA) that encodes α-galactosidase A (α-Gal A). The iminosugar AT1001 (GR181413A, migalastat hydrochloride, 1-deoxygalactonojirimycin) is a pharmacological chaperone that selectively binds and stabilizes α-Gal A, increasing total cellular levels and activity for some mu...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Wu X,Katz E,Della Valle MC,Mascioli K,Flanagan JJ,Castelli JP,Schiffmann R,Boudes P,Lockhart DJ,Valenzano KJ,Benjamin ER

    更新日期:2011-08-01 00:00:00

  • A novel frameshift mutation (141delT) in exon 1 of the 21-hydroxylase gene (CYP21) in a patient with the salt wasting form of congenital adrenal hyperplasia. Mutation in brief no. 255. Online.

    abstract::Congenital adrenal hyperplasia (CAH) is a common autosomal recessive disease with a wide range of clinical manifestation. In 90-95% of the cases it is caused by 21-hydroxylase deficiency (OMIM #201910) due to mutations of the CYP21 gene (GDB Accession #M12792). In most cases the CYP21-inactivating point mutations are ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Krone N,Braun A,Roscher AA,Schwarz HP

    更新日期:1999-01-01 00:00:00

  • EYS is a major gene for rod-cone dystrophies in France.

    abstract::Autosomal-recessive retinitis pigmentosa (arRP) was recently associated with mutations in a novel gene EYS, spanning over 2 Mb, making it the largest known gene expressed in the human eye. The purpose of this study was to establish the prevalence and nature of EYS mutations in a clinically well-characterized cohort of...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Audo I,Sahel JA,Mohand-Saïd S,Lancelot ME,Antonio A,Moskova-Doumanova V,Nandrot EF,Doumanov J,Barragan I,Antinolo G,Bhattacharya SS,Zeitz C

    更新日期:2010-05-01 00:00:00

  • BRCA2 germline mutations in Cypriot patients with familial breast/ovarian cancer.

    abstract::Germline mutations in the BRCA2 gene have been shown to be associated with familial female and male breast cancer. Mutations occur throughout the entire coding region of the gene, and there is considerable ethnic and geographical diversity in the deleterious mutations detected in different populations. No data exist o...

    journal_title:Human mutation

    pub_type: 杂志文章,多中心研究


    authors: Hadjisavvas A,Charalambous E,Adamou A,Christodoulou CG,Kyriacou K

    更新日期:2003-02-01 00:00:00

  • Impaired development of neural-crest cell-derived organs and intellectual disability caused by MED13L haploinsufficiency.

    abstract::MED13L is a component subunit of the Mediator complex, an important regulator of transcription that is highly conserved across eukaryotes. Here, we report MED13L disruption in a translocation t(12;19) breakpoint of a patient with Pierre-Robin syndrome, moderate intellectual disability, craniofacial anomalies, and musc...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Utami KH,Winata CL,Hillmer AM,Aksoy I,Long HT,Liany H,Chew EG,Mathavan S,Tay SK,Korzh V,Sarda P,Davila S,Cacheux V

    更新日期:2014-11-01 00:00:00

  • Novel TSC2 mutations and decreased expression of tuberin in cultured tumor cells with an insertion mutation.

    abstract::Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by hamartomas in many organs. Two genes responsible for TSC, TSC1 and TSC2, were recently identified. TSC1 and TSC2 encode the proteins hamartin and tuberin, respectively, and 337 different mutations have been reported in these genes thus...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Feng JH,Yamamoto T,Nanba E,Ninomiya H,Oka A,Ohno K

    更新日期:2004-04-01 00:00:00

  • Novel homozygous truncating variants in ZMYND15 causing severe oligozoospermia and their implications for male infertility.

    abstract::Sequence variants of ZMYND15 cause azoospermia in humans, but they have not yet been reported in infertile men with severe oligozoospermia (SO). We performed whole-exome and Sanger sequencing to identify suspected causative variants in 414 idiopathic participating infertile men with SO or azoospermia. Three novel homo...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Hu TY,Zhang H,Meng LL,Yuan SM,Tu CF,Du J,Lu GX,Lin G,Nie HC,Tan YQ

    更新日期:2020-11-10 00:00:00

  • Heterozygous missense mutations in NFATC1 are associated with atrioventricular septal defect.

    abstract::Atrioventricular septal defect (AVSD) may occur as part of a complex disorder (e.g., Down syndrome, heterotaxy), or as isolate cardiac defect. Multiple lines of evidence support a role of calcineurin/NFAT signaling in AVSD, and mutations in CRELD1, a protein functioning as a regulator of calcineurin/NFAT signaling hav...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Ferese R,Bonetti M,Consoli F,Guida V,Sarkozy A,Lepri FR,Versacci P,Gambardella S,Calcagni G,Margiotti K,Piceci Sparascio F,Hozhabri H,Mazza T,Digilio MC,Dallapiccola B,Tartaglia M,Marino B,Hertog JD,De Luca A

    更新日期:2018-10-01 00:00:00

  • A fast polymerase chain reaction-mediated strategy for introducing repeat expansions into CAG-repeat containing genes.

    abstract::We describe a simple method for expanding CAG trinucleotides in CAG-repeat containing genes which, in contrast to other techniques, leaves the original gene sequence intact. Here, we expanded the CAG stretches of a plasmid clone containing the cDNA of the SCA3/MJD gene from 22 CAG up to > 130 CAG repeats using polymer...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Laccone F,Maiwald R,Bingemann S

    更新日期:1999-01-01 00:00:00

  • Allele-specific measurement of low-density lipoprotein receptor transcript levels.

    abstract::We have developed an assay for allele-specific determination of low-density lipoprotein receptor (LDLR) mRNAs. Transcript levels are measured by reverse transcription (RT), PCR, and electrophoresis on an automatic DNA sequencer using fluorescence-labeled primers and direct quantitation of the allele-specific RT-PCR pr...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Jensen LG,Jensen HK,Heath F,Eiberg H,Kjeldsen M,Faergeman O,Kølvraa S,Bolund L,Gregersen N

    更新日期:1996-01-01 00:00:00

  • Chemical chaperone therapy: chaperone effect on mutant enzyme and cellular pathophysiology in β-galactosidase deficiency.

    abstract::β-Galactosidase deficiency is a group of lysosomal lipid storage disorders with an autosomal recessive trait. It causes two clinically different diseases, G(M1) -gangliosidosis and Morquio B disease. It is caused by heterogeneous mutations in the GLB1 gene coding for the lysosomal acid β-galactosidase. We have previou...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Higaki K,Li L,Bahrudin U,Okuzawa S,Takamuram A,Yamamoto K,Adachi K,Paraguison RC,Takai T,Ikehata H,Tominaga L,Hisatome I,Iida M,Ogawa S,Matsuda J,Ninomiya H,Sakakibara Y,Ohno K,Suzuki Y,Nanba E

    更新日期:2011-07-01 00:00:00

  • Mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) variants in American and Japanese populations.

    abstract::M6P/IGF2R encodes a multifunctional protein involved in lysosomal enzyme trafficking, fetal organogenesis, tumor suppression, and cytotoxic T cell-induced apoptosis. M6P/IGF2R is imprinted and expressed only from the maternally inherited allele in marsupials and rodents. In contrast, humans were initially reported to ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Killian JK,Oka Y,Jang HS,Fu X,Waterland RA,Sohda T,Sakaguchi S,Jirtle RL

    更新日期:2001-01-01 00:00:00

  • Familial lipoprotein lipase (LPL) deficiency: a catalogue of LPL gene mutations identified in 20 patients from the UK, Sweden, and Italy.

    abstract::The aim of this study was to identify mutations in the lipoprotein lipase (LPL) gene in 20 unrelated patients with familial lipoprotein deficiency (FLLD) and to investigate the genotype/phenotype relationship. The previously reported G188E mutation (Monsalve et al., J Clin Invest 86:728-734, 1990) was screened for and...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Mailly F,Palmen J,Muller DP,Gibbs T,Lloyd J,Brunzell J,Durrington P,Mitropoulos K,Betteridge J,Watts G,Lithell H,Angelico F,Humphries SE,Talmud PJ

    更新日期:1997-01-01 00:00:00

  • Mutation update: TGFBI pathogenic and likely pathogenic variants in corneal dystrophies.

    abstract::Human transforming growth factor β-induced (TGFBI), is a gene responsible for various corneal dystrophies. TGFBI produces a protein called TGFBI, which is involved in cell adhesion and serves as a recognition sequence for integrins. An alteration in cell surface interactions could be the underlying cause for the progr...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Kheir V,Cortés-González V,Zenteno JC,Schorderet DF

    更新日期:2019-06-01 00:00:00

  • Clinical spectrum of LIG4 deficiency is broadened with severe dysmaturity, primordial dwarfism, and neurological abnormalities.

    abstract::DNA double-strand break repair via non-homologous end joining (NHEJ) is involved in recombination of immunoglobulin and T-cell receptor genes. Mutations in NHEJ components result in syndromes that are characterized by microcephaly and immunodeficiency. We present a patient with lymphopenia, extreme radiosensitivity, s...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: IJspeert H,Warris A,van der Flier M,Reisli I,Keles S,Chishimba S,van Dongen JJ,van Gent DC,van der Burg M

    更新日期:2013-12-01 00:00:00

  • CAPN5 genetic inactivation phenotype supports therapeutic inhibition trials.

    abstract::Small molecule pharmacological inhibition of dominant human genetic disease is a feasible treatment that does not rely on the development of individual, patient-specific gene therapy vectors. However, the consequences of protein inhibition as a clinical therapeutic are not well-studied. In advance of human therapeutic...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Wert KJ,Koch SF,Velez G,Hsu CW,Mahajan M,Bassuk AG,Tsang SH,Mahajan VB

    更新日期:2019-12-01 00:00:00

  • Genetic and functional analyses of ZIC3 variants in congenital heart disease.

    abstract::Mutations in zinc-finger in cerebellum 3 (ZIC3) result in heterotaxy or isolated congenital heart disease (CHD). The majority of reported mutations cluster in zinc-finger domains. We previously demonstrated that many of these lead to aberrant ZIC3 subcellular trafficking. A relative paucity of N- and C-terminal mutati...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Cowan J,Tariq M,Ware SM

    更新日期:2014-01-01 00:00:00

  • Phylogenetic and in silico structural analysis of the Parkinson disease-related kinase PINK1.

    abstract::Parkinson disease (PD) is the second most common neurodegenerative disorder and is characterized by the loss of dopaminergic neurons in the substantia nigra. Mutations in PINK1 were shown to cause recessive familial PD, and today are proposed to be associated with the disease via mitochondrial dysfunction and oxidativ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Cardona F,Sánchez-Mut JV,Dopazo H,Pérez-Tur J

    更新日期:2011-04-01 00:00:00

  • Targeted next-generation sequencing can replace Sanger sequencing in clinical diagnostics.

    abstract::Mutation detection through exome sequencing allows simultaneous analysis of all coding sequences of genes. However, it cannot yet replace Sanger sequencing (SS) in diagnostics because of incomplete representation and coverage of exons leading to missing clinically relevant mutations. Targeted next-generation sequencin...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Sikkema-Raddatz B,Johansson LF,de Boer EN,Almomani R,Boven LG,van den Berg MP,van Spaendonck-Zwarts KY,van Tintelen JP,Sijmons RH,Jongbloed JD,Sinke RJ

    更新日期:2013-07-01 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

  • An XML-based interchange format for genotype-phenotype data.

    abstract::Recent advances in high-throughput genotyping and phenotyping have accelerated the creation of pharmacogenomic data. Consequently, the community requires standard formats to exchange large amounts of diverse information. To facilitate the transfer of pharmacogenomics data between databases and analysis packages, we ha...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Whirl-Carrillo M,Woon M,Thorn CF,Klein TE,Altman RB

    更新日期:2008-02-01 00:00:00

  • Mutations in severe combined immune deficiency (SCID) due to JAK3 deficiency.

    abstract::During the last 10 years, an increasing number of genes have been identified whose abnormalities account for primary immunodeficiencies, with defects in development and/or function of the immune system. Among them is the JAK3-gene, encoding for a tyrosine kinase that is functionally coupled to cytokine receptors which...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Notarangelo LD,Mella P,Jones A,de Saint Basile G,Savoldi G,Cranston T,Vihinen M,Schumacher RF

    更新日期:2001-10-01 00:00:00

  • Mutation detection in the duplicated region of the polycystic kidney disease 1 (PKD1) gene in PKD1-linked Australian families.

    abstract::Screening for disease-causing mutations in the duplicated region of the PKD1 gene was performed in 17 unrelated Australian individuals with PKD1-linked autosomal dominant polycystic kidney disease. Exons 2-21 and 23-34 were assayed using PKD1-specific PCR amplification and direct sequencing. We have identified 12 nove...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: McCluskey M,Schiavello T,Hunter M,Hantke J,Angelicheva D,Bogdanova N,Markoff A,Thomas M,Dworniczak B,Horst J,Kalaydjieva L

    更新日期:2002-03-01 00:00:00

  • VIPdb, a genetic Variant Impact Predictor Database.

    abstract::Genome sequencing identifies vast number of genetic variants. Predicting these variants' molecular and clinical effects is one of the preeminent challenges in human genetics. Accurate prediction of the impact of genetic variants improves our understanding of how genetic information is conveyed to molecular and cellula...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Hu Z,Yu C,Furutsuki M,Andreoletti G,Ly M,Hoskins R,Adhikari AN,Brenner SE

    更新日期:2019-09-01 00:00:00

  • Structural and biochemical consequences of NF1 associated nontruncating mutations in the Sec14-PH module of neurofibromin.

    abstract::Neurofibromatosis type 1 (NF1) is a common genetic disorder caused by alterations in the tumor suppressor gene NF1. Clinical manifestations include various neural crest derived tumors, pigmentation anomalies, bone deformations, and learning disabilities. NF1 encodes the Ras specific GTPase activating protein (RasGAP) ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Welti S,Kühn S,D'Angelo I,Brügger B,Kaufmann D,Scheffzek K

    更新日期:2011-02-01 00:00:00

  • Somatic MED12 Nonsense Mutation Escapes mRNA Decay and Reveals a Motif Required for Nuclear Entry.

    abstract::MED12 is a key component of the transcription-regulating Mediator complex. Specific missense and in-frame insertion/deletion mutations in exons 1 and 2 have been identified in uterine leiomyomas, breast tumors, and chronic lymphocytic leukemia. Here, we characterize the first MED12 5' end nonsense mutation (c.97G>T, p...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Heikkinen T,Kämpjärvi K,Keskitalo S,von Nandelstadh P,Liu X,Rantanen V,Pitkänen E,Kinnunen M,Kuusanmäki H,Kontro M,Turunen M,Mäkinen N,Taipale J,Heckman C,Lehti K,Mustjoki S,Varjosalo M,Vahteristo P

    更新日期:2017-03-01 00:00:00

  • Identification of two novel LDL receptor gene defects in French-Canadian pediatric population: mutational analysis and biochemical studies.

    abstract::Familial hypercholesterolemia (FH) is at least twofold more prevalent in French Canadians from Québec than in most Western populations. Although our recent data confirmed this high frequency of heterozygous FH in our pediatric population with hypercholesterolemia, none of the five established molecular defects for the...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Assouline L,Leitersdorf E,Lambert M,Reshef A,Feoli-Fonseca JC,Levy E

    更新日期:1997-01-01 00:00:00

  • A novel nonstop mutation in TYMP does not induce nonstop mRNA decay in a MNGIE patient with severe neuropathy.

    abstract::The cellular quality control systems enable surveillance and selective degradation of nonsense, nonstop, and no-go mRNAs. In the case of nonstop mRNA, different mechanisms of nonstop-mediated decay (NSD) have been described for bacteria, yeast and mammals, but the molecular consequences of nonstop mutations have been ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Torres-Torronteras J,Rodriguez-Palmero A,Pinós T,Accarino A,Andreu AL,Pintos-Morell G,Martíí R

    更新日期:2011-04-01 00:00:00