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


: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 homozygote, belonging to FH families were tested. In all cases, previous genetic analysis and/or LDL receptor fibroblast assay had shown that the disease was due to defects in the LDLR gene. Out of the nine mutations expected, one nonsense mutation in exon 2 and six missense mutations were identified in exons 3, 6, 8, 11, and 15. Two of the latter were found in exon 6. In each family, cosegregation of the base substitution and the disease was observed. Ninety-five control subjects were screened for the presence of the six missense mutations. None was detected, implying that the mutations identified are deleterious. Our results indicate that the SSCP analysis of amplified genomic DNA fragments can be successfully used to rapidly screen mutation containing exons in large genes. Furthermore, all these mutations are newly described and demonstrate heterogeneity of LDLR gene mutations responsible for FH in the French population, as in other reported Caucasian populations.


Hum Mutat


Human mutation


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





Has Abstract,Author List Incomplete


1992-01-01 00:00:00












  • A functional variant in the miR-142 promoter modulating its expression and conferring risk of Alzheimer disease.

    abstract::Noncoding RNAs have been widely recognized as essential mediators of gene regulation. However, in contrast to protein-coding genes, much less is known about the influence of noncoding RNAs on human diseases. Here we examined the association of genetic variants located in primary microRNA sequences and long noncoding R...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Ghanbari M,Munshi ST,Ma B,Lendemeijer B,Bansal S,Adams HH,Wang W,Goth K,Slump DE,van den Hout MCGN,van IJcken WFJ,Bellusci S,Pan Q,Erkeland SJ,de Vrij FMS,Kushner SA,Ikram MA

    更新日期:2019-11-01 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

  • GRIN database: A unified and manually curated repertoire of GRIN variants.

    abstract::Glutamatergic neurotransmission is crucial for brain development, wiring neuronal function, and synaptic plasticity mechanisms. Recent genetic studies showed the existence of autosomal dominant de novo GRIN gene variants associated with GRIN-related disorders (GRDs), a rare pediatric neurological disorder caused by N-...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: García-Recio A,Santos-Gómez A,Soto D,Julia-Palacios N,García-Cazorla À,Altafaj X,Olivella M

    更新日期:2020-11-30 00:00:00

  • Rapid detection of submicroscopic chromosomal rearrangements in children with multiple congenital anomalies using high density oligonucleotide arrays.

    abstract::Chromosomal rearrangements such as microdeletions and interstitial duplications are the underlying cause of many human genetic disorders. These disorders can manifest in the form of multiple congenital anomalies (MCA), which are a significant cause of morbidity and mortality in children. The major limitations of cytog...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Ming JE,Geiger E,James AC,Ciprero KL,Nimmakayalu M,Zhang Y,Huang A,Vaddi M,Rappaport E,Zackai EH,Shaikh TH

    更新日期:2006-05-01 00:00:00

  • Identification and computationally-based structural interpretation of naturally occurring variants of human protein C.

    abstract::Protein C (PC) is a key regulator of blood clotting and inflammation. Its inherited deficiency is associated with venous thromboembolism, and recombinant activated PC is currently used to increase survival in severe sepsis. The molecular basis of inherited PC deficiency is heterogeneous. Due to its multiple physiologi...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Rovida E,Merati G,D'Ursi P,Zanardelli S,Marino F,Fontana G,Castaman G,Faioni EM

    更新日期:2007-04-01 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

  • A founder mutation (R254X) of SLC22A5 (OCTN2) in Chinese primary carnitine deficiency patients.

    abstract::Mutations in the SLC22A5 gene, which encodes for the plasma membrane carnitine transporter OCTN2, cause primary carnitine deficiency (PCD). After our first report of OCTN2 mutations in Chinese, three more Chinese PCD patients were identified. The parents of these families were non-consanguineous and these families wer...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Tang NL,Hwu WL,Chan RT,Law LK,Fung LM,Zhang WM

    更新日期:2002-09-01 00:00:00

  • Pancreatic insufficiency and pulmonary disease in German and Slavic cystic fibrosis patients with the R347P mutation.

    abstract::Cystic fibrosis (CF) is caused by mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) that codes for a cAMP-regulated chloride channel. The R347P is a missense mutation located within the first membrane spanning domain (MSD1) of the CFTR protein. This mutation occurs with an overal...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Varon R,Stuhrmann M,Macek M Jr,Kufardjieva A,Angelicheva D,Magdorf K,Jordanova A,Savov A,Wahn U,Macek M

    更新日期:1995-01-01 00:00:00

  • Novel allele containing a 190C>T nonsynonymous substitution in the N-acetyltransferase (NAT2) gene.

    abstract::N-acetyltransferase (NAT2) is an enzyme involved in detoxification of various carcinogens. The gene is highly polymorphic with a number of alleles, and is also known as acetylator phenotypes: the fast, intermediate and slow acetylators. In this report, we describe a novel NAT2 allele, which was found in the allele typ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Shishikura K,Hohjoh H,Tokunaga K

    更新日期:2000-06-01 00:00:00

  • Structural assessment of single amino acid mutations: application to TP53 function.

    abstract::Single amino acid substitution is the type of protein alteration most related to human diseases. Current studies seek primarily to distinguish neutral mutations from harmful ones. Very few methods offer an explanation of the final prediction result in terms of the probable structural or functional effect on the protei...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Yip YL,Zoete V,Scheib H,Michielin O

    更新日期:2006-09-01 00:00:00

  • BBS7 and TTC8 (BBS8) mutations play a minor role in the mutational load of Bardet-Biedl syndrome in a multiethnic population.

    abstract::Bardet Biedl syndrome is a genetically heterogeneous ciliopathy with fourteen genes currently identified. To date, mutations in BBS7 and TTC8 (BBS8) were reported in 4.2% and 2.8% of BBS families respectively. We sequenced the coding regions of BBS7 and TTC8 in 35 BBS families of diverse ancestral backgrounds. In addi...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Bin J,Madhavan J,Ferrini W,Mok CA,Billingsley G,Héon E

    更新日期:2009-07-01 00:00:00

  • High-resolution DNA melting analysis: advancements and limitations.

    abstract::Recent advances in fluorescent dyes, methods, instruments and software for DNA melting analysis have created versatile new tools for variant scanning and genotyping. High resolution melting analysis (HRM or HRMA) is faster, simpler, and less expensive than alternative approaches requiring separations or labeled probes...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Wittwer CT

    更新日期:2009-06-01 00:00:00

  • Quantitative allele-specific PCR: demonstration of age-associated accumulation in human tissues of the A-->G mutation at nucleotide 3243 in mitochondrial DNA.

    abstract::We have developed an improved allele-specific polymerase chain reaction (AS-PCR) procedure that can selectively amplify mutant DNA sequences (which differ from the normal sequences by a single base pair) in the presence of large excess of normal sequences. We applied this procedure to quantification of mutant molecule...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Liu VW,Zhang C,Linnane AW,Nagley P

    更新日期:1997-01-01 00:00:00

  • Exon scanning of the entire TSC2 gene for germline mutations in 40 unrelated patients with tuberous sclerosis.

    abstract::Tuberous sclerosis complex (TSC) is a dominantly inherited multisystem disorder resulting in the development of hamartomatous growths in many organs. Genetic heterogeneity has been demonstrated linking the familial cases to either TSC1 at 9q34.3, or TSC2 at 16p13.3. About two-thirds of the TSC cases are sporadic and a...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Beauchamp RL,Banwell A,McNamara P,Jacobsen M,Higgins E,Northrup H,Short P,Sims K,Ozelius L,Ramesh V

    更新日期:1998-01-01 00:00:00

  • A Review of Whole-Exome Sequencing Efforts Toward Hereditary Breast Cancer Susceptibility Gene Discovery.

    abstract::Inherited genetic risk factors contribute toward breast cancer (BC) onset. BC risk variants can be divided into three categories of penetrance (high, moderate, and low) that reflect the probability of developing the disease. Traditional BC susceptibility gene discovery approaches that searched for high- and moderate-r...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Chandler MR,Bilgili EP,Merner ND

    更新日期:2016-09-01 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

  • Five novel mutations in the lysosomal sialidase gene (NEU1) in type II sialidosis patients and assessment of their impact on enzyme activity and intracellular targeting using adenovirus-mediated expression.

    abstract::Sialidosis is an autosomal recessive disease resulting from a deficiency of lysosomal sialidase. Type II sialidosis is a rare disease characterized clinically by hydrops fetalis, hepatosplenomegaly, and severe psychomotor retardation. Genomic DNA from four unrelated sialidosis patients was screened for mutations withi...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Pattison S,Pankarican M,Rupar CA,Graham FL,Igdoura SA

    更新日期:2004-01-01 00:00:00

  • Identification of 36 novel Jagged1 (JAG1) mutations in patients with Alagille syndrome.

    abstract::Alagille syndrome (AGS) is an autosomal dominant disorder characterized by five major symptoms: cholestasis, vertebral deformity, heart malformations, ocular defects and peculiar facial appearance. The previously described Jagged1 (JAG1) gene on chromosome 20p12 has been identified as being responsible for AGS. JAG1 e...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Röpke A,Kujat A,Gräber M,Giannakudis J,Hansmann I

    更新日期:2003-01-01 00:00:00

  • A Novel KCNJ13 Nonsense Mutation and Loss of Kir7.1 Channel Function Causes Leber Congenital Amaurosis (LCA16).

    abstract::Mutations in the KCNJ13 gene that encodes the inwardly rectifying potassium channel Kir7.1 cause snowflake vitreoretinal degeneration (SVD) and leber congenital amaurosis (LCA). Kir7.1 controls the microenvironment between the photoreceptors and the retinal pigment epithelium (RPE) and also contributes to the function...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Pattnaik BR,Shahi PK,Marino MJ,Liu X,York N,Brar S,Chiang J,Pillers DA,Traboulsi EI

    更新日期:2015-07-01 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

  • 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

  • Combined NGS approaches identify mutations in the intraflagellar transport gene IFT140 in skeletal ciliopathies with early progressive kidney Disease.

    abstract::Ciliopathies are genetically heterogeneous disorders characterized by variable expressivity and overlaps between different disease entities. This is exemplified by the short rib-polydactyly syndromes, Jeune, Sensenbrenner, and Mainzer-Saldino chondrodysplasia syndromes. These three syndromes are frequently caused by m...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Schmidts M,Frank V,Eisenberger T,Al Turki S,Bizet AA,Antony D,Rix S,Decker C,Bachmann N,Bald M,Vinke T,Toenshoff B,Di Donato N,Neuhann T,Hartley JL,Maher ER,Bogdanović R,Peco-Antić A,Mache C,Hurles ME,Joksić I,G

    更新日期:2013-05-01 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 large deletion mutation in the CFTR gene (3120+1Kbdel8.6Kb): a founder mutation in the Palestinian Arabs. Mutation in brief no. 231. Online.

    abstract::A deletion mutation of 8.6Kb in the CFTR gene, spanning the exons 17a, 17b and 18 was identified in 4 homozygous unrelated Palestinian CF patients. The patients were of various ethnic subgroups including Muslims, Christians and Druze. The deletion breakpoint occurred within an identical 4bp sequence in introns 16 and ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Lerer I,Laufer-Cahana A,Rivlin JR,Augarten A,Abeliovich D

    更新日期:1999-01-01 00:00:00

  • Identification of novel mutations in PEX2, PEX6, PEX10, PEX12, and PEX13 in Zellweger spectrum patients.

    abstract::Mutations in each of the 13 identified human PEX genes are known to cause a peroxisomal biogenesis defect (PBD). Affected patients can be divided into two broad clinical spectra: the Zellweger spectrum, which accounts for about 80% of PBD patients, and the rhizomelia chondrodysplasia punctata (RCDP) spectrum. The clin...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Krause C,Rosewich H,Thanos M,Gärtner J

    更新日期:2006-11-01 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

  • 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

  • Postzygotic single-nucleotide mosaicisms contribute to the etiology of autism spectrum disorder and autistic traits and the origin of mutations.

    abstract::The roles and characteristics of postzygotic single-nucleotide mosaicisms (pSNMs) in autism spectrum disorders (ASDs) remain unclear. In this study of the whole exomes of 2,361 families in the Simons Simplex Collection, we identified 1,248 putative pSNMs in children and 285 de novo SNPs in children with detectable par...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Dou Y,Yang X,Li Z,Wang S,Zhang Z,Ye AY,Yan L,Yang C,Wu Q,Li J,Zhao B,Huang AY,Wei L

    更新日期:2017-08-01 00:00:00

  • STAC3 variants cause a congenital myopathy with distinctive dysmorphic features and malignant hyperthermia susceptibility.

    abstract::SH3 and cysteine-rich domain-containing protein 3 (STAC3) is an essential component of the skeletal muscle excitation-contraction coupling (ECC) machinery, though its role and function are not yet completely understood. Here, we report 18 patients carrying a homozygous p.(Trp284Ser) STAC3 variant in addition to a pati...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Zaharieva IT,Sarkozy A,Munot P,Manzur A,O'Grady G,Rendu J,Malfatti E,Amthor H,Servais L,Urtizberea JA,Neto OA,Zanoteli E,Donkervoort S,Taylor J,Dixon J,Poke G,Foley AR,Holmes C,Williams G,Holder M,Yum S,Medne L

    更新日期:2018-12-01 00:00:00

  • BAK1 gene variation and abdominal aortic aneurysms.

    abstract::We sought to examine the role of genetics in the multifactorial disease, abdominal aortic aneurysm (AAA), by studying sequence variation in the BAK1 gene (BAK1) that codes for an apoptotic-promoting protein, as chronic apoptosis activation has been linked to AAA development and progression. BAK1 abdominal aorta cDNA f...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Gottlieb B,Chalifour LE,Mitmaker B,Sheiner N,Obrand D,Abraham C,Meilleur M,Sugahara T,Bkaily G,Schweitzer M

    更新日期:2009-07-01 00:00:00