Novel CASK mutations in cases with syndromic microcephaly.


:Mutations in CASK cause a wide spectrum of phenotypes in humans ranging from mild X-linked intellectual disability to a severe microcephaly (MC) and pontocerebellar hypoplasia syndrome. Nevertheless, predicting pathogenicity and phenotypic consequences of novel CASK mutations through the exclusive consideration of genetic information and population-based data remains a challenge. Using whole exome sequencing, we identified four novel CASK mutations in individuals with syndromic MC. To understand the functional consequences of the different point mutations on the development of MC and cerebellar defects, we established a transient loss-of-function zebrafish model, and demonstrate recapitulation of relevant neuroanatomical phenotypes. Furthermore, we utilized in vivo complementation studies to demonstrate that the three point mutations confer a loss-of-function effect. This work endorses zebrafish as a tractable model to rapidly assess the effect of novel CASK variants on brain development.


Hum Mutat


Human mutation


Cristofoli F,Devriendt K,Davis EE,Van Esch H,Vermeesch JR




Has Abstract


2018-07-01 00:00:00












  • Novel mutations in African American patients with glycogen storage disease Type II. Mutations in brief no. 209. Online.

    abstract::The infantile form of GSD II (an inherited deficiency of the lysosomal enzyme, acid alpha-glucosidase, Pompe disease) is a severe and invariably fatal disease characterized by a rapidly progressive generalized hypotonia, hepatomegaly, and cardiomegaly. We have recently demonstrated that African American patients share...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Raben N,Lee E,Lee L,Hirschhorn R,Plotz PH

    更新日期:1999-01-01 00:00:00

  • Clinically relevant variants - identifying, collecting, interpreting, and disseminating: the 2013 annual scientific meeting of the Human Genome Variation Society.

    abstract::The dramatic advances in genetic sequencing technologies used in research laboratories are now entering the clinic, and applications of whole-genome and whole-exome sequencing to disease diagnosis, predisposition, and treatment will soon be commonplace. However, the standards and methods for identifying clinically rel...

    journal_title:Human mutation



    authors: Stanley CM,Sunyaev SR,Greenblatt MS,Oetting WS

    更新日期:2014-04-01 00:00:00

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

    abstract::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 ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: 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

    更新日期:2018-09-01 00:00:00

  • Comprehensive profiling of BRCA1 and BRCA2 variants in breast and ovarian cancer in Chinese patients.

    abstract::The identification and interpretation of germline BRCA1/2 variants become increasingly important in breast and ovarian cancer (OC) treatment. However, there is no comprehensive analysis of the germline BRCA1/2 variants in a Chinese population. Here we performed a systematic review and meta-analysis on such variants fr...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Gao X,Nan X,Liu Y,Liu R,Zang W,Shan G,Gai F,Zhang J,Li L,Cheng G,Song L

    更新日期:2020-03-01 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

  • Mutation update for the CSB/ERCC6 and CSA/ERCC8 genes involved in Cockayne syndrome.

    abstract::Cockayne syndrome is an autosomal recessive multisystem disorder characterized principally by neurological and sensory impairment, cachectic dwarfism, and photosensitivity. This rare disease is linked to mutations in the CSB/ERCC6 and CSA/ERCC8 genes encoding proteins involved in the transcription-coupled DNA repair p...

    journal_title:Human mutation

    pub_type: 杂志文章,meta分析


    authors: Laugel V,Dalloz C,Durand M,Sauvanaud F,Kristensen U,Vincent MC,Pasquier L,Odent S,Cormier-Daire V,Gener B,Tobias ES,Tolmie JL,Martin-Coignard D,Drouin-Garraud V,Heron D,Journel H,Raffo E,Vigneron J,Lyonnet S,Murday

    更新日期:2010-02-01 00:00:00

  • Mutations and polymorphisms in the familial early-onset breast cancer (BRCA1) gene. Breast Cancer Information Core.

    abstract::Mutations in the familial early-onset breast cancer gene (BRCA1) account for approximately 2-5% of all breast cancer cases (Easton et al., 1993). Since the isolation of the BRCA1 gene in 1994, many mutations have been identified. We report here a total of 254 BRCA1 mutations, 132 (52%) of which are unique. These repre...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Couch FJ,Weber BL

    更新日期:1996-01-01 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

  • A mutation update for the PCDH19 gene causing early-onset epilepsy in females with an unusual expression pattern.

    abstract::The PCDH19 gene consists of six exons encoding a 1,148 amino acid transmembrane protein, Protocadherin 19, which is involved in brain development. Heterozygous pathogenic variants in this gene are inherited in an unusual X-linked dominant pattern in which heterozygous females are affected, while hemizygous males are t...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Niazi R,Fanning EA,Depienne C,Sarmady M,Abou Tayoun AN

    更新日期:2019-03-01 00:00:00

  • Cantú syndrome resulting from activating mutation in the KCNJ8 gene.

    abstract::ATP-sensitive potassium (KATP ) channels, composed of inward-rectifying potassium channel subunits (Kir6.1 and Kir6.2, encoded by KCNJ8 and KCNJ11, respectively) and regulatory sulfonylurea receptor (SUR1 and SUR2, encoded by ABCC8 and ABCC9, respectively), couple metabolism to excitability in multiple tissues. Mutati...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Cooper PE,Reutter H,Woelfle J,Engels H,Grange DK,van Haaften G,van Bon BW,Hoischen A,Nichols CG

    更新日期:2014-07-01 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

  • Palindrome-mediated and replication-dependent pathogenic structural rearrangements within the NF1 gene.

    abstract::Palindromic sequences can form hairpin structures or cruciform extrusions, which render them susceptible to genomic rearrangements. A 197-bp long palindromic AT-rich repeat (PATRR17) is located within intron 40 of the neurofibromatosis type 1 (NF1) gene (17q11.2). Through comprehensive NF1 analysis, we identified six ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Hsiao MC,Piotrowski A,Alexander J,Callens T,Fu C,Mikhail FM,Claes KB,Messiaen L

    更新日期:2014-07-01 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

  • Screening of the PKD1 duplicated region reveals multiple single nucleotide polymorphisms and a de novo mutation in Hellenic polycystic kidney disease families.

    abstract::Mutations in the PKD1 gene account for approximately 85% of cases with autosomal dominant polycystic kidney disease (ADPKD1; MIM# 601313), which is considered one of the most frequent monogenic disorders, with a frequency of approximately 1:1000. The main symptom is the formation of fluid-filled cysts in the kidneys a...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Koptides M,Mean R,Demetriou K,Constantinides R,Pierides A,Harris PC,Deltas CC

    更新日期:2000-08-01 00:00:00

  • Functional assessment of TSC2 variants identified in individuals with tuberous sclerosis complex.

    abstract::Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in the TSC1 or TSC2 genes. The TSC1 and TSC2 gene products, TSC1 and TSC2, form a complex that inhibits the mammalian target of rapamycin (mTOR) complex 1 (TORC1). Here, we investigate the effects of 78 TSC2 variants identified in i...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Hoogeveen-Westerveld M,Ekong R,Povey S,Mayer K,Lannoy N,Elmslie F,Bebin M,Dies K,Thompson C,Sparagana SP,Davies P,van Eeghen AM,Thiele EA,van den Ouweland A,Halley D,Nellist M

    更新日期:2013-01-01 00:00:00

  • Two novel missense mutations of the OCTN2 gene (W283R and V446F) in a patient with primary systemic carnitine deficiency.

    abstract::Primary systemic carnitine deficiency (SCD) is an autosomal recessive disorder of fatty acid oxidation caused by defective cellular carnitine transport. The disease is characterized by metabolic derangement simulating Reye's syndrome, hypoglcaemia, progressive cardiomyopathy and skeletal myopathy. Recently, it was sho...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Mayatepek E,Nezu J,Tamai I,Oku A,Katsura M,Shimane M,Tsuji A

    更新日期:2000-01-01 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

  • Mutations in BTD causing biotinidase deficiency.

    abstract::Biotinidase (BTD) is the only enzyme that can cleave biocytin, a product of the proteolytic digestion of holocarboxylases. Profound BTD deficiency (less than 10% mean normal activity in serum) is an autosomal recessive disorder that can result in neurological and cutaneous abnormalities. Both the cDNA and the genomic ...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Hymes J,Stanley CM,Wolf B

    更新日期:2001-11-01 00:00:00

  • Deletions in the 3' part of the NFIX gene including a recurrent Alu-mediated deletion of exon 6 and 7 account for previously unexplained cases of Marshall-Smith syndrome.

    abstract::Marshall-Smith syndrome (MSS) is a very rare malformation syndrome characterized by typical craniofacial anomalies, abnormal osseous maturation, developmental delay, failure to thrive, and respiratory difficulties. Mutations in the nuclear factor 1/X gene (NFIX) were recently identified as the cause of MSS. In our stu...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Schanze D,Neubauer D,Cormier-Daire V,Delrue MA,Dieux-Coeslier A,Hasegawa T,Holmberg EE,Koenig R,Krueger G,Schanze I,Seemanova E,Shaw AC,Vogt J,Volleth M,Reis A,Meinecke P,Hennekam RC,Zenker M

    更新日期:2014-09-01 00:00:00

  • Congenital myasthenic syndrome due to mutations in MUSK suggests that the level of MuSK phosphorylation is crucial for governing synaptic structure.

    abstract::MUSK encodes the muscle-specific receptor tyrosine kinase (MuSK), a key component of the agrin-LRP4-MuSK-DOK7 signaling pathway, which is essential for the formation and maintenance of highly specialized synapses between motor neurons and muscle fibers. We report a patient with severe early-onset congenital myasthenic...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Rodríguez Cruz PM,Cossins J,Cheung J,Maxwell S,Jayawant S,Herbst R,Waithe D,Kornev AP,Palace J,Beeson D

    更新日期:2020-03-01 00:00:00

  • Pyrosequencing: an accurate detection platform for single nucleotide polymorphisms.

    abstract::Pyrosequencing, a non-electrophoretic method for DNA sequencing, is emerging as a popular platform for analysis of single nucleotide polymorphisms (SNPs). This technology has the advantage of accuracy, ease-of-use, and high flexibility for different applications. Here, we review the methodology and the use of this tec...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Fakhrai-Rad H,Pourmand N,Ronaghi M

    更新日期:2002-05-01 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

  • Propionic acidemia: analysis of mutant propionyl-CoA carboxylase enzymes expressed in Escherichia coli.

    abstract::Deficiency of propionyl-CoA carboxylase (PCC) results in propionic acidemia, an autosomal recessive disorder characterized by ketoacidosis sufficiently severe to cause neonatal death. PCC is involved in the catabolism of branched-chain amino acids, odd-chain fatty acids, and cholesterol. The enzyme is a biotin-depende...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Chloupkova M,Maclean KN,Alkhateeb A,Kraus JP

    更新日期:2002-06-01 00:00:00

  • Identification of nine novel arylsulfatase a (ARSA) gene mutations in patients with metachromatic leukodystrophy (MLD).

    abstract::Metachromatic leukodystrophy (MLD) is a rare autosomal recessive disorder caused by mutations of the arylsulfatase A (ARSA) gene. We have investigated more than fifty MLD patients using allele-specific PCR assays to detect the pseudodeficiency (PD) allele and several common MLD mutations, followed by comprehensive nuc...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Eng B,Nakamura LN,O'Reilly N,Schokman N,Nowaczyk MM,Krivit W,Waye JS

    更新日期:2003-11-01 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

  • Multiexon skipping leading to an artificial DMD protein lacking amino acids from exons 45 through 55 could rescue up to 63% of patients with Duchenne muscular dystrophy.

    abstract::Approximately two-thirds of Duchenne muscular dystrophy (DMD) patients show intragenic deletions ranging from one to several exons of the DMD gene and leading to a premature stop codon. Other deletions that maintain the translational reading frame of the gene result in the milder Becker muscular dystrophy (BMD) form o...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Béroud C,Tuffery-Giraud S,Matsuo M,Hamroun D,Humbertclaude V,Monnier N,Moizard MP,Voelckel MA,Calemard LM,Boisseau P,Blayau M,Philippe C,Cossée M,Pagès M,Rivier F,Danos O,Garcia L,Claustres M

    更新日期:2007-02-01 00:00:00

  • Stability related bias in residues replacing glycines within the collagen triple helix (Gly-Xaa-Yaa) in inherited connective tissue disorders.

    abstract::A missense mutation leading to the replacement of one Gly in the (Gly-Xaa-Yaa)n repeat of the collagen triple helix can cause a range of heritable connective tissue disorders that depend on the gene in which the mutation occurs. Osteogenesis imperfecta results from mutations in type I collagen, Ehlers-Danlos syndrome ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Persikov AV,Pillitteri RJ,Amin P,Schwarze U,Byers PH,Brodsky B

    更新日期:2004-10-01 00:00:00

  • Novel Tay-Sachs disease mutations from China.

    abstract::We describe three HEXA mutations associated with infantile Tay-Sachs disease (TSD) in three unrelated nonconsanguineous Chinese families. Novel mutations were found in two of these families. The third is a previously reported mutation (G-->A transition at nt 1444) (Nakano et al., 1988). Direct sequencing of PCR produc...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Akalin N,Shi HP,Vavougios G,Hechtman P,Lo W,Scriver CR,Mahuran D,Kaplan F

    更新日期:1992-01-01 00:00:00

  • Network-Informed Gene Ranking Tackles Genetic Heterogeneity in Exome-Sequencing Studies of Monogenic Disease.

    abstract::Genetic heterogeneity presents a significant challenge for the identification of monogenic disease genes. Whole-exome sequencing generates a large number of candidate disease-causing variants and typical analyses rely on deleterious variants being observed in the same gene across several unrelated affected individuals...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Dand N,Schulz R,Weale ME,Southgate L,Oakey RJ,Simpson MA,Schlitt T

    更新日期:2015-12-01 00:00:00

  • Functional analysis and classification of homozygous and hypomorphic ABCA4 variants associated with Stargardt macular degeneration.

    abstract::Stargardt macular degeneration (Stargardt disease 1 [STGD1]) is caused by mutations in the gene encoding ABCA4, an ATP-binding cassette protein that transports N-retinylidene-phosphatidylethanolamine (N-Ret-PE) across photoreceptor membranes. Reduced ABCA4 activity results in retinoid accumulation leading to photorece...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Curtis SB,Molday LL,Garces FA,Molday RS

    更新日期:2020-11-01 00:00:00