Functional characterization of the TSC2 c.3598C>T (p.R1200W) missense mutation that co-segregates with tuberous sclerosis complex in mildly affected kindreds.


:Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by a combination of neurological symptoms and hamartomatous growths, and caused by mutations in the TSC1 and TSC2 genes. Overall, TSC2 mutations are associated with a more severe disease phenotype. We identified the c.3598C>T (R1200W) change in the TSC2 gene in seven different families. The clinical phenotypes in the families were mild, characterized by mild skin lesions, remitting epilepsy and a lack of severe mental retardation or major organ involvement. Functional analysis of the TSC2 R1200W variant, and four other TSC2 missense variants associated with a mild TSC phenotype, confirmed that the changes disrupted the TSC1-TSC2 function. Interestingly however, in each case, the TSC1-TSC2 interaction was not affected by the amino acid substitution.


Clin Genet


Clinical genetics


Wentink M,Nellist M,Hoogeveen-Westerveld M,Zonnenberg B,van der Kolk D,van Essen T,Park SM,Woods G,Cohn-Hokke P,Brussel W,Smeets E,Brooks A,Halley D,van den Ouweland A,Maat-Kievit A




Has Abstract


2012-05-01 00:00:00












  • Genetic analysis of the glucose-6-phosphatase mutation of type 1a glycogen storage disease in a Chinese family.

    abstract::Type 1a glycogen storage disease (GSD) is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase (G6Pase). Polymerase chain reaction (PCR) and nucleotide sequence analysis were used to identify the location and nature of mutations at the G6Pase locus in two siblings affected with typ...

    journal_title:Clinical genetics

    pub_type: 杂志文章


    authors: Lee WJ,Lee HM,Chi CS,Shu SG,Lin LY,Lin WH

    更新日期:1996-10-01 00:00:00

  • Single mandibular incisor in a patient with del (18p) anomaly.

    abstract::A single mandibular incisor and an unusually narrow mandible and tongue were noted in an 8-year-old moderately retarded boy with 18p- (45, XY, der dic (18) (18qter-p11.2::22p 11.2-qter). While a single maxillary incisor, considered a minor feature of holoprosencephaly, was reported in three cases of 18p-, reduction of...

    journal_title:Clinical genetics

    pub_type: 杂志文章


    authors: Pfeiffer RA,Hertrich K,Cohen M

    更新日期:1994-12-01 00:00:00

  • Autosomal dominant IFIH1 gain-of-function mutations cause Aicardi-Goutières syndrome.

    abstract::Aicardi-Goutières Syndrome is caused by IFIH1 mutations Oda et al.(2014) The American Journal of Human Genetics 95(1): 121-125. Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling Rice et al.(2014) Nature Genetics 46(5): 503-510. ...

    journal_title:Clinical genetics

    pub_type: 评论,杂志文章


    authors: Diamond J

    更新日期:2014-11-01 00:00:00

  • Assessing risk assessment: genetic testing and screening for complex disease.

    abstract::This paper reports on the presentations from the second session of a 2-day workshop on genetic diversity and science communication, organized by the Institute of Genetics. The four talks in this session (by Sarah Cunningham-Burley, Gail Geller, Michael Hayden, and Theresa Marteau) focused on the topic of risk assessme...

    journal_title:Clinical genetics



    authors: Cox SM

    更新日期:2006-11-01 00:00:00

  • The personal experience of juvenile Huntington's disease: an interpretative phenomenological analysis of parents' accounts of the primary features of a rare genetic condition.

    abstract::There has been a paucity of research into the psychosocial impact of juvenile Huntington's disease (JHD) on the child and the family. The study reported here is part of larger project that aimed to address this and investigate the social and health care needs of those affected by JHD. Ten semistructured interviews wit...

    journal_title:Clinical genetics

    pub_type: 杂志文章


    authors: Smith JA,Brewer HM,Eatough V,Stanley CA,Glendinning NW,Quarrell OW

    更新日期:2006-06-01 00:00:00

  • Genetic regulatory pathways of split-hand/foot malformation.

    abstract::Split-hand/foot malformation (SHFM) is caused by mutations in TP63, DLX5, DLX6, FGF8, FGFR1, WNT10B, and BHLHA9. The clinical features of SHFM caused by mutations of these genes are not distinguishable. This implies that in normal situations these SHFM-associated genes share an underlying regulatory pathway that is in...

    journal_title:Clinical genetics

    pub_type: 杂志文章,评审


    authors: Kantaputra PN,Carlson BM

    更新日期:2019-01-01 00:00:00

  • Selective immunodeficiency with defect in interferon-gamma induction in two sibs with recurrent infections.

    abstract::Phytohaemagglutinin induces interferon-gamma synthesis in lymphocyte cultures from healthy individuals. We report two sibs with recurrent infections, selective IgA deficiency, and reduced blast transformation index under PHA-stimulation, without interferon-gamma response. ...

    journal_title:Clinical genetics

    pub_type: 杂志文章


    authors: Tzoneva M,Ganev V,Galabov A,Georgieva K

    更新日期:1988-06-01 00:00:00

  • Novel mutations of the ferroportin gene (SLC40A1): analysis of 56 consecutive patients with unexplained iron overload.

    abstract::The aim of this study was to search for SLC40A1 mutations in iron overloaded patients, which tested negative for HFE mutations and other iron-related genes. After a careful differential diagnosis, we selected 56 patients with unexplained iron overload whose phenotype could suggest the ferroportin disease. Iron overloa...

    journal_title:Clinical genetics

    pub_type: 杂志文章


    authors: Pelucchi S,Mariani R,Salvioni A,Bonfadini S,Riva A,Bertola F,Trombini P,Piperno A

    更新日期:2008-02-01 00:00:00

  • First direct evidence of involvement of a homozygous loss-of-function variant in the EPS15L1 gene underlying split-hand/split-foot malformation.

    abstract::Split-hand/split-foot malformation (SHFM) is a severe form of congenital limb deformity characterized by the absence of 1 or more digits and/or variable degree of median clefts of hands and feet. The present study describes an investigation of a consanguineous family of Pakistani origin segregating SHFM in an autosoma...

    journal_title:Clinical genetics

    pub_type: 杂志文章


    authors: Umair M,Ullah A,Abbas S,Ahmad F,Basit S,Ahmad W

    更新日期:2018-03-01 00:00:00

  • Anthropometric and craniofacial patterns in mentally retarded males with emphasis on the fragile X syndrome.

    abstract::Anthropometric and craniofacial profile patterns indicating the percent difference from the overall mean were developed on 34 physical parameters with 31 white, mentally retarded males (23 adults and 8 children) with the fra(X) syndrome matched for age with 31 white, mentally retarded males without a known cause of th...

    journal_title:Clinical genetics

    pub_type: 杂志文章


    authors: Butler MG,Pratesi R,Watson MS,Breg WR,Singh DN

    更新日期:1993-09-01 00:00:00

  • Saethre-Chotzen syndrome (ACS III) in four generations.

    abstract::The acrocephalosyndactylies (ACS) are a group of inherited disorders characterized by premature fusion of cranial sutures in association with abnormalities of the hands and feet. Based on their clinical features, different types of ACS have been described. We here report on a family with 9 individuals affected with AC...

    journal_title:Clinical genetics

    pub_type: 杂志文章


    authors: Niemann-Seyde SC,Eber SW,Zoll B

    更新日期:1991-10-01 00:00:00

  • Next-generation sequencing of Chinese stage IV lung cancer patients reveals an association between EGFR mutation status and survival outcome.

    abstract::Large-scale genomic characterization of non-small cell lung cancer (NSCLC) has revealed several putative oncogenic driver mutations that may constitute druggable therapeutic targets. However, there are little data to suggest that such gene alterations have clinical relevance. Over 12 consecutive months, tumor biopsy s...

    journal_title:Clinical genetics

    pub_type: 杂志文章


    authors: Li F,Du X,Zhang H,Ju T,Chen C,Qu Q,Zhang X,Qi L,Lizée G

    更新日期:2017-03-01 00:00:00

  • The role of long non-coding RNAs in drug resistance of cancer.

    abstract::Long non-coding RNAs (lncRNAs), a class of long RNAs, are longer than 200 nucleotides in length but lack protein-coding capacity. LncRNAs, as critical genomic regulators, are involved in genomic imprinting regulation, histone modification and gene expression regulation as well as tumor initiation and progression. Howe...

    journal_title:Clinical genetics

    pub_type: 杂志文章,评审


    authors: Zhang HD,Jiang LH,Zhong SL,Li J,Sun DW,Hou JC,Wang DD,Zhou SY,Tang JH

    更新日期:2021-01-01 00:00:00

  • The prevalence of chromosome abnormalities among mentally retarded persons in a geographically delimited area of Denmark.

    abstract::A cytogenetic survey of an unselected group of mentally retarded persons in a geographically limited area was made in order to establish the frequency of chromosome abnormalities within this group. In the area there were 2,157 patients, both institutionalized and living at home. A chromosome analysis was performed in ...

    journal_title:Clinical genetics

    pub_type: 杂志文章


    authors: Rasmussen K,Nielsen J,Dahl G

    更新日期:1982-11-01 00:00:00

  • Cryptic chromosomal rearrangement screening in 30 patients with mental retardation and dysmorphic features.

    abstract::Mental retardation affects 1-3% of the general population, and the genetic causes in many cases are unknown. Cytogenetically undetected chromosomal imbalances have been indicated as an explanation. Nowadays, due to the development of molecular cytogenetic techniques, it is possible to identify cryptic rearrangements i...

    journal_title:Clinical genetics

    pub_type: 杂志文章


    authors: Rodriguez-Revenga L,Badenas C,Sánchez A,Mallolas J,Carrió A,Pedrinaci S,Barrionuevo JL,Milà M

    更新日期:2004-01-01 00:00:00

  • Paracentric inversion of chromosome 9 with schizoaffective disorder.

    abstract::A 36-year-old man with schizoaffective disorder was found to have a de novo 46 XY inv (9) (q31.2q34.3). Phenotypical abnormalities are short stature, depressed nasal bridge, hypertelorism and slender shoulders. Paracentric inversion of chromosome 9 is a rare chromosome aberration. This case suggests a new candidate re...

    journal_title:Clinical genetics

    pub_type: 杂志文章


    authors: Inayama Y,Yoneda H,Fukushima K,Sakai J,Asaba H,Sakai T

    更新日期:1997-01-01 00:00:00

  • Agenesis of the corpus callosum, infantile spasms, spastic quadriplegia, microcephaly and severe mental retardation in three siblings.

    abstract::A sibship consisting of three siblings, one male and two females with unrelated parents, showed a clinical syndrome including: infantile spasms with hypsarrhythmia, microcephaly, severe mental retardation and spastic quadriplegia. The pneumoencephalogram performed in two sibs showed agenesis of the corpus callosum and...

    journal_title:Clinical genetics

    pub_type: 杂志文章


    authors: Cao A,Cianchetti C,Signorini E,Loi M,Sanna G,De Virgiliis S

    更新日期:1977-11-01 00:00:00

  • Somatic segregation and Fanconi anemia.

    abstract::A case of Fanconi anemia with terminal acute leukemia is reported. Clones with chromosome abnormalities were observed in bone marrow cells. The patterns of marker chromosome distribution in these clones suggests the occurrence of a somatic segregation mechanism. ...

    journal_title:Clinical genetics

    pub_type: 杂志文章


    authors: Berger R,Bussel A,Schenmetzler C

    更新日期:1977-06-01 00:00:00

  • Heredity in personality disorders--an overview.

    abstract::The concept of personality disorders is based on deviant personality traits in both the DSM-III-R and ICD-10 classifications. A diagnosis of personality disorder can be made reliably with structured interviews. Many individuals are diagnosed with more than one personality disorder, and other mental disorders are often...

    journal_title:Clinical genetics

    pub_type: 杂志文章,评审


    authors: Dahl AA

    更新日期:1994-07-01 00:00:00

  • Genetic variation in MKL2 and decreased downstream PCTAIRE1 expression in extreme, fatal primary human microcephaly.

    abstract::The genetic mechanisms driving normal brain development remain largely unknown. We performed genomic and immunohistochemical characterization of a novel, fatal human phenotype including extreme microcephaly with cerebral growth arrest at 14-18 weeks gestation in three full sisters born to healthy, non-consanguineous p...

    journal_title:Clinical genetics

    pub_type: 杂志文章


    authors: Ramos EI,Bien-Willner GA,Li J,Hughes AE,Giacalone J,Chasnoff S,Kulkarni S,Parmacek M,Cole FS,Druley TE

    更新日期:2014-05-01 00:00:00

  • Genomic copy number alterations in non-syndromic hearing loss.

    abstract::Genetic heterogeneity has made the identification of genes related to hearing impairment a challenge. In the absence of a clear phenotypic aetiology, recurrence risk estimates are often based on family segregation and may be imprecise. We profiled by oligonucleotide array-CGH patients presenting non-syndromic hearing ...

    journal_title:Clinical genetics

    pub_type: 杂志文章


    authors: Rosenberg C,Freitas ÉL,Uehara DT,Auricchio MTBM,Costa SS,Oiticica J,Silva AG,Krepischi AC,Mingroni-Netto RC

    更新日期:2016-04-01 00:00:00

  • Rhizomelic chondrodysplasia punctata and survival beyond one year: a review of the literature and five case reports.

    abstract::Rhizomelic chondrodysplasia punctata (RCDP), a peroxisomal disorder, is considered to be a lethal neonatal autosomal recessive chondrodysplasia. We report five patients, three of whom survived beyond 1 year, and we summarize the findings in 21 patients from a literature review who survived beyond 1 year. In those pati...

    journal_title:Clinical genetics

    pub_type: 杂志文章,评审


    authors: Wardinsky TD,Pagon RA,Powell BR,McGillivray B,Stephan M,Zonana J,Moser A

    更新日期:1990-08-01 00:00:00

  • Three novel patients with epileptic encephalopathy due to biallelic mutations in the PLCB1 gene.

    abstract::Biallelic mutations in the PLCB1 gene, encoding for a phospholipase C beta isoform strongly expressed in the brain, have been reported to cause infantile epileptic encephalopathy in only four children to date. We report here three additional patients to delineate the phenotypic and genotypic characteristics of the dis...

    journal_title:Clinical genetics

    pub_type: 杂志文章


    authors: Desprairies C,Valence S,Maurey H,Helal SI,Weckhuysen S,Soliman H,Mefford HC,Spentchian M,Héron D,Leguern E,Nava C,Bouilleret V,Moretti R,Mignot C

    更新日期:2020-03-01 00:00:00

  • Pharmacogenetics: A strategy for personalized medicine for autoimmune diseases.

    abstract::For many years, a considerable number of patients with autoimmune diseases (ADs) have suffered from a lack of drug response and drug-related toxicity. Despite the emergence of new therapeutic options such as biological agents, patients continue to struggle with these problems. Unfortunately, new challenges, including ...

    journal_title:Clinical genetics

    pub_type: 杂志文章,评审


    authors: Tavakolpour S,Darvishi M,Ghasemiadl M

    更新日期:2018-03-01 00:00:00

  • Digenic inheritance of an autosomal recessive hypotrichosis in two consanguineous pedigrees.

    abstract::Hypotrichosis is a human hereditary hair loss disorder in which affected individuals show sparse to complete absence of hair on scalp and/or on different body parts. To date, at least eight isolated autosomal recessive and dominant forms of hypotrichosis loci have been mapped on different human chromosomes, and the co...

    journal_title:Clinical genetics

    pub_type: 杂志文章


    authors: Basit S,Wali A,Aziz A,Muhammad N,Jelani M,Ahmad W

    更新日期:2011-03-01 00:00:00

  • Chromosomes in retinoblastoma patients.

    abstract::In a series of eight patients with retinoblastoma, one was found to have a reciprocal translocation of chromosomes 1 and 13. The breakpoint on chromosome 13 is at band q12, which suggests that the retinoblastoma locus is less distal than previously thought. ...

    journal_title:Clinical genetics

    pub_type: 杂志文章


    authors: Davison EV,Gibbons B,Aherne GE,Roberts DF

    更新日期:1979-06-01 00:00:00

  • Charcot-Marie-Tooth type 1B neuropathy: third mutation of serine 63 codon in the major peripheral myelin glycoprotein PO gene.

    abstract::We report studies on two patients (a mother and her daughter) presenting with a Charcot-Marie-Tooth type 1 (CMT1) phenotype: low nerve conduction velocities of 13-15 m/s and an early onset at the age of walking. DNA analysis of the gene coding for the major peripheral myelin protein PO showed a new point mutation in e...

    journal_title:Clinical genetics

    pub_type: 杂志文章


    authors: Blanquet-Grossard F,Pham-Dinh D,Dautigny A,Latour P,Bonnebouche C,Corbillon E,Chazot G,Vandenberghe A

    更新日期:1995-12-01 00:00:00

  • Current knowledge of medical complications in adults with achondroplasia: A scoping review.

    abstract::This article provides an overview of the current knowledge on medical complications, health characteristics, and psychosocial issues in adults with achondroplasia. We have used a scoping review methodology particularly recommended for mapping and summarizing existing research evidence, and to identify knowledge gaps. ...

    journal_title:Clinical genetics

    pub_type: 杂志文章,评审


    authors: Fredwall SO,Maanum G,Johansen H,Snekkevik H,Savarirayan R,Lidal IB

    更新日期:2020-01-01 00:00:00

  • Reduced plasma concentrations of total, low density lipoprotein and high density lipoprotein cholesterol in patients with Gaucher type I disease.

    abstract::Plasma lipid and serum apoprotein concentrations were determined in twenty-nine individuals with Gaucher type I disease. Plasma total cholesterol, low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol were all significantly reduced in the patients with Gaucher disease compared to a g...

    journal_title:Clinical genetics

    pub_type: 杂志文章


    authors: Ginsberg H,Grabowski GA,Gibson JC,Fagerstrom R,Goldblatt J,Gilbert HS,Desnick RJ

    更新日期:1984-08-01 00:00:00

  • Linkage studies on Marinesco-Sjøgren syndrome and hypergonadotropic hypogonadism.

    abstract::Marinesco-Sjøgren syndrome and hypergonadotropic hypogonadism were observed in two kindreds, and they were found to occur togetherin 9 out of 10 affected individuals. The last patient had Marinesco-Sjøgren syndrome without manifestations of hypogonadism, and similar findings were observed in two affected sisters from ...

    journal_title:Clinical genetics

    pub_type: 杂志文章


    authors: Skre H,Berg K

    更新日期:1977-01-01 00:00:00