Elucidating the genetic architecture of Adams-Oliver syndrome in a large European cohort.


:Adams-Oliver syndrome (AOS) is a rare developmental disorder, characterized by scalp aplasia cutis congenita (ACC) and transverse terminal limb defects (TTLD). Autosomal dominant forms of AOS are linked to mutations in ARHGAP31, DLL4, NOTCH1 or RBPJ, while DOCK6 and EOGT underlie autosomal recessive inheritance. Data on the frequency and distribution of mutations in large cohorts are currently limited. The purpose of this study was therefore to comprehensively examine the genetic architecture of AOS in an extensive cohort. Molecular diagnostic screening of 194 AOS/ACC/TTLD probands/families was conducted using next-generation and/or capillary sequencing analyses. In total, we identified 63 (likely) pathogenic mutations, comprising 56 distinct and 22 novel mutations, providing a molecular diagnosis in 30% of patients. Taken together with previous reports, these findings bring the total number of reported disease variants to 63, with a diagnostic yield of 36% in familial cases. NOTCH1 is the major contributor, underlying 10% of AOS/ACC/TTLD cases, with DLL4 (6%), DOCK6 (6%), ARHGAP31 (3%), EOGT (3%), and RBPJ (2%) representing additional causality in this cohort. We confirm the relevance of genetic screening across the AOS/ACC/TTLD spectrum, highlighting preliminary but important genotype-phenotype correlations. This cohort offers potential for further gene identification to address missing heritability.


Hum Mutat


Human mutation


Meester JAN,Sukalo M,Schröder KC,Schanze D,Baynam G,Borck G,Bramswig NC,Duman D,Gilbert-Dussardier B,Holder-Espinasse M,Itin P,Johnson DS,Joss S,Koillinen H,McKenzie F,Morton J,Nelle H,Reardon W,Roll C,Salih MA,Sa




Has Abstract


2018-09-01 00:00:00












  • BRCA1 and BRCA2 mutations in Russian familial breast cancer.

    abstract::We have screened index cases from 25 Russian breast/ovarian cancer families for germ-line mutations in all coding exons of the BRCA1 and BRCA2 genes, using multiplex heteroduplex analysis. In addition we tested 22 patients with breast cancer diagnosed before age 40 without family history and 6 patients with bilateral ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Tereschenko IV,Basham VM,Ponder BA,Pharoah PD

    更新日期:2002-02-01 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

  • Natural haplotypes in the regulatory sequences affect human alcohol dehydrogenase 1C (ADH1C) gene expression.

    abstract::Human alcohol dehydrogenases (ADHs) play important roles in metabolizing alcohol, and several lines of evidence suggest that variations in ADH genes affect the risk for alcoholism. Differences in regulatory sequences could affect the expression of ADH genes and thereby modify the risk for alcoholism. To explore this i...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Chen HJ,Tian H,Edenberg HJ

    更新日期:2005-02-01 00:00:00

  • Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype.

    abstract::Uridine-diphosphoglucuronate glucuronosyltransferases (UGTs) are a family of enzymes that conjugate various endogenous and exogenous compounds with glucuronic acid and facilitate their excretion in the bile. Bilirubin-UGT(1) (UGT1A1) is the only isoform that significantly contributes to the conjugation of bilirubin. L...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Kadakol A,Ghosh SS,Sappal BS,Sharma G,Chowdhury JR,Chowdhury NR

    更新日期:2000-10-01 00:00:00

  • Fanconi anemia A due to a novel frameshift mutation in hotspot motifs: lack of FANCA protein.

    abstract::Homozygosity for a frameshift mutation at codon 1213 of FANCA gene was identified in a Turkish patient. Immunoprecipitation-western blot analysis showed the complete absence of the FANCA protein band. This novel mutation, a deletion of T at position 3639 in exon 37 (3639delT), is responsible for the disease and causes...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Balta G,de Winter JP,Kayserili H,Pronk JC,Joenje H

    更新日期:2000-06-01 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

  • Transport, enzymatic activity, and stability of mutant sulfamidase (SGSH) identified in patients with mucopolysaccharidosis type III A.

    abstract::Mucopolysaccharidosis type IIIA (MPSIIIA) is an autosomal recessive lysosomal storage disease caused by mutations in the N-sulfoglucosamine sulfohydrolase gene (SGSH; encoding sulfamidase, also sulphamidase) leading to the lysosomal accumulation and urinary excretion of heparan sulfate. Considerable variation in the o...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Muschol N,Storch S,Ballhausen D,Beesley C,Westermann JC,Gal A,Ullrich K,Hopwood JJ,Winchester B,Braulke T

    更新日期:2004-06-01 00:00:00

  • Detection of more than 94% cystic fibrosis mutations in a sample of Belgian population and identification of four novel mutations.

    abstract::We have analysed 194 Belgian CF chromosomes using a variety of techniques: delta F508 was detected by polyacrylamide gel electrophoresis; dot blotting of PCR products was used to identify the mutations G542X, 1717-1 G-->A, and N1303K; molecular defects in exons 2, 3, 4, 5, 6b, 7, 11, 12, 13, 14a, 14b, 17b, 19, 20, and...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Mercier B,Lissens W,Audrézet MP,Bonduelle M,Liebaers I,Ferec C

    更新日期:1993-01-01 00:00:00

  • Gene-specific criteria for PTEN variant curation: Recommendations from the ClinGen PTEN Expert Panel.

    abstract::The ClinGen PTEN Expert Panel was organized by the ClinGen Hereditary Cancer Clinical Domain Working Group to assemble clinicians, researchers, and molecular diagnosticians with PTEN expertise to develop specifications to the 2015 ACMG/AMP Sequence Variant Interpretation Guidelines for PTEN variant interpretation. We ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Mester JL,Ghosh R,Pesaran T,Huether R,Karam R,Hruska KS,Costa HA,Lachlan K,Ngeow J,Barnholtz-Sloan J,Sesock K,Hernandez F,Zhang L,Milko L,Plon SE,Hegde M,Eng C

    更新日期:2018-11-01 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

  • Truncating somatic mutation in exon 15 of the APC gene is a rare event in human breast carcinomas. Mutations in brief no. 179. Online.

    abstract::Inactivation of the adenomatous polyposis coli (APC) gene is an early event in sporadic colorectal cancer. Somatic mutations have also been detected in cancers of the stomach, pancreas, thyroid, ovary and breast. Over 95% of the mutations reported in the APC gene are frameshift and nonsense mutations. The large exon 1...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Sørlie T,Bukholm I,Børresen-Dale AL

    更新日期:1998-01-01 00:00:00

  • Tissue distribution of the ND4/11778 mutation in heteroplasmic lineages with Leber hereditary optic neuropathy.

    abstract::Leber hereditary optic neuropathy (LHON) is a maternally inherited eye disease most commonly caused by mitochondrial DNA (mtDNA) point mutation at position 11778, 3460, or 14484. Approximately 14% of families show heteroplasmy for the pathogenic mutations but little is known about the mutational burden in different ti...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Juvonen V,Nikoskelainen E,Lamminen T,Penttinen M,Aula P,Savontaus ML

    更新日期:1997-01-01 00:00:00

  • Apolipoprotein A-IV polymorphism in the Hungarian population: gene frequencies, effect on lipid levels, and sequence of two new variants.

    abstract::The genetic polymorphism of human apolipoprotein A-IV was investigated in Hungarian blood donors (n = 202) by isoelectric focusing (IEF) of plasma samples followed by immunoblotting. The frequency of apo A-IV alleles was f(A-IV1) = 0.95, f(A-IV2) = 0.039 and f(A-IV3) = 0.002. This frequency distribution is significant...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Menzel HJ,Dieplinger H,Sandholzer C,Karádi I,Utermann G,Császár A

    更新日期:1995-01-01 00:00:00

  • The spectrum of ELANE mutations and their implications in severe congenital and cyclic neutropenia.

    abstract::Neutrophil elastase gene (ELANE) mutations are responsible for the majority of cases of severe congenital neutropenia (CN) and cyclic neutropenia (CyN). We screened CN (n = 395) or CyN (n = 92) patients for ELANE mutations and investigated the impact of mutations on mRNA expression, protein expression, and activity. W...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Germeshausen M,Deerberg S,Peter Y,Reimer C,Kratz CP,Ballmaier M

    更新日期:2013-06-01 00:00:00

  • Homologous loci DXYS156X and DXYS156Y contain a polymorphic pentanucleotide repeat (TAAAA)n and map to human X and Y chromosomes.

    abstract::We report the isolation and characterization of a polymorphic pentanucleotide repeat (TAAAA)n, which was mapped to human chromosomes X and Y (loci DXYS156X and DXYS156Y) by PCR amplification of DNA from a monochromosomal somatic cell hybrid panel (NIGMS panel 2). The (TAAAA)n repeat of loci DXYS156 occurs within a hum...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Chen H,Lowther W,Avramopoulos D,Antonarakis SE

    更新日期:1994-01-01 00:00:00

  • Biochemical and molecular characterization of 18 patients with pyridoxine-dependent epilepsy and mutations of the antiquitin (ALDH7A1) gene.

    abstract::Patients with pyridoxine dependent epilepsy (PDE) present with early-onset seizures resistant to common anticonvulsants. According to the benefit of pyridoxine (vitamin B(6)) and recurrence of seizures on pyridoxine withdrawal, patients so far have been classified as having definite, probable, or possible PDE. Recentl...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Plecko B,Paul K,Paschke E,Stoeckler-Ipsiroglu S,Struys E,Jakobs C,Hartmann H,Luecke T,di Capua M,Korenke C,Hikel C,Reutershahn E,Freilinger M,Baumeister F,Bosch F,Erwa W

    更新日期:2007-01-01 00:00:00

  • Bayesian approach to discovering pathogenic SNPs in conserved protein domains.

    abstract::The success rate of association studies can be improved by selecting better genetic markers for genotyping or by providing better leads for identifying pathogenic single nucleotide polymorphisms (SNPs) in the regions of linkage disequilibrium with positive disease associations. We have developed a novel algorithm to p...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Cai Z,Tsung EF,Marinescu VD,Ramoni MF,Riva A,Kohane IS

    更新日期:2004-08-01 00:00:00

  • Exploring the use of molecular dynamics in assessing protein variants for phenotypic alterations.

    abstract::With the advent of rapid sequencing technologies, making sense of all the genomic variations that we see among us has been a major challenge. A plethora of algorithms and methods exist that try to address genome interpretation through genotype-phenotype linkage analysis or evaluating the loss of function/stability mut...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Garg A,Pal D

    更新日期:2019-09-01 00:00:00

  • Analysis of CDKN1C in Beckwith Wiedemann syndrome.

    abstract::In this study we have examined 32 patients with Beckwith Wiedemann Syndrome (BWS) for mutations affecting the CDKN1C gene, including seven cases of familial BWS. Mutations were not detected in the coding region of the CDKN1C gene in any individual with BWS. However in two patients, two G/A base substitutions at adjace...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Algar E,Brickell S,Deeble G,Amor D,Smith P

    更新日期:2000-01-01 00:00:00

  • Novel TMPRSS6 mutations associated with iron-refractory iron deficiency anemia (IRIDA).

    abstract::Mutations leading to abrogation of matriptase-2 proteolytic activity in humans are associated with an iron-refractory iron deficiency anemia (IRIDA) due to elevated hepcidin levels. In this paper we describe 12 IRIDA patients belonging to 7 unrelated families and identify 10 (9 novel) TMPRSS6 mutations spread along th...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: De Falco L,Totaro F,Nai A,Pagani A,Girelli D,Silvestri L,Piscopo C,Campostrini N,Dufour C,Al Manjomi F,Minkov M,Van Vuurden DG,Feliu A,Kattamis A,Camaschella C,Iolascon A

    更新日期:2010-05-01 00:00:00

  • Base substitutions in the human dystrophin gene: detection by using the single-strand conformation polymorphism (SSCP) technique.

    abstract::We have established the experimental conditions to screen twenty regions of the dystrophin gene using the method of single-strand conformational polymorphism (SSCP) analysis. The aim of this study was to identify point mutations in patients with Duchenne or Becker muscular dystrophy (DMD or BMD) who have no gross DNA ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Tuffery S,Moine P,Demaille J,Claustres M

    更新日期:1993-01-01 00:00:00

  • Human Variome Project country nodes: documenting genetic information within a country.

    abstract::The Human Variome Project (http://www.humanvariomeproject.org) is an international effort aiming to systematically collect and share information on all human genetic variation. The two main pillars of this effort are gene/disease-specific databases and a network of Human Variome Project Country Nodes. The latter are n...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Patrinos GP,Smith TD,Howard H,Al-Mulla F,Chouchane L,Hadjisavvas A,Hamed SA,Li XT,Marafie M,Ramesar RS,Ramos FJ,de Ravel T,El-Ruby MO,Shrestha TR,Sobrido MJ,Tadmouri G,Witsch-Baumgartner M,Zilfalil BA,Auerbach AD,Ca

    更新日期:2012-11-01 00:00:00

  • Spectrum of GJB2 mutations in Turkey comprises both Caucasian and Oriental variants: roles of parental consanguinity and assortative mating.

    abstract::Considerable differences exist for the spectrum of GJB2 mutations in different populations. Screening for the c.35delG mutation in 256 independent probands, 154 multiplex (familial) and 102 simplex (sporadic), coming from different regions of Turkey revealed 37 (14.5%) homozygotes. The allele frequency of c.35delG ran...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Tekin M,Duman T,Boğoçlu G,Incesulu A,Comak E,Ilhan I,Akar N

    更新日期:2003-05-01 00:00:00

  • The 185delAG mutation (c.68_69delAG) in the BRCA1 gene triggers translation reinitiation at a downstream AUG codon.

    abstract::The 185delAG mutation (c.68_69delAG; ter39) in the BRCA1 gene is a founder Jewish Ashkenazi mutation that is carried by 1% of this population and has been identified in thousands of breast or ovarian cancer patients. We have previously described that transcripts bearing this mutation, as well as transcripts bearing th...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Buisson M,Anczuków O,Zetoune AB,Ware MD,Mazoyer S

    更新日期:2006-10-01 00:00:00

  • Determination of 30 X-linked adrenoleukodystrophy mutations, including 15 not previously described.

    abstract::X-linked Adrenoleukodystrophy (X-ALD) is the most frequent peroxisomal disease. It mainly involves the nervous system white matter, adrenal cortex and testes. Several distinct clinical phenotypes are known. The principal biochemical abnormality is the accumulation of saturated very-long-chain fatty acids (VLCFAs : > C...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Lachtermacher MB,Seuánez HN,Moser AB,Moser HW,Smith KD

    更新日期:2000-01-01 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

  • Molecular basis of congenital insensitivity to pain with anhidrosis (CIPA): mutations and polymorphisms in TRKA (NTRK1) gene encoding the receptor tyrosine kinase for nerve growth factor.

    abstract::Congenital insensitivity to pain with anhidrosis (CIPA), also referred to as hereditary sensory and autonomic neuropathy type IV (HSAN-IV), is an autosomal recessive hereditary disorder characterized by recurrent episodic fever, anhidrosis (inability to sweat), absence of reaction to noxious stimuli, self-mutilating b...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Indo Y

    更新日期:2001-12-01 00:00:00

  • Impaired calmodulin binding of myosin-7A causes autosomal dominant hearing loss (DFNA11).

    abstract::Both myosin 7A (MYO7A) and calmodulin (CaM) are required for transduction and adaptation processes in inner ear hair cells. We identified a novel heterozygous missense mutation (c.2557C>T; p.R853C) in a family with autosomal dominant non-syndromic hearing loss that changes an evolutionarily invariant residue of the fi...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Bolz H,Bolz SS,Schade G,Kothe C,Mohrmann G,Hess M,Gal A

    更新日期:2004-09-01 00:00:00

  • Somatic mutations of the first 14 exons of APC in hamartomatous polyps of the colon.

    abstract::Although hamartomatous or hyperplastic polyps are rarely accompanied by adenomatous or carcinomatous foci, the role of APC (MIM# 175100) mutations in these polyps is not clear. The neoplastic potential of these polyps was assessed with regard to somatic mutation of the first 14 exons of APC. DNA from 14 hamartomatous ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Kim JC,Roh SA,Kim HC,Yu CS,Lee DH,Ahn BY,Kim KM,Yang SK,Kang GH,Beck NE,Bodmer WF

    更新日期:1999-10-01 00:00:00

  • Sensitive multistep clinical molecular screening of 180 unrelated individuals with retinoblastoma detects 36 novel mutations in the RB1 gene.

    abstract::Retinoblastoma (RB) is a neoplasm of retinal origin caused by mutations in RB1, the retinoblastoma tumor suppressor gene. To facilitate genetics counseling and patient management, we adopted a multistep molecular screening assay for detecting RB1 mutations. This assay included DNA sequencing to identify mutations with...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Nichols KE,Houseknecht MD,Godmilow L,Bunin G,Shields C,Meadows A,Ganguly A

    更新日期:2005-06-01 00:00:00