SLC7A9 mutations in all three cystinuria subtypes

Slides:

Advertisements

Similar presentations

Epidermolysis Bullosa: Novel and De Novo Premature Termination Codon and Deletion Mutations in the Plectin Gene Predict Late-Onset Muscular Dystrophy

Advertisements

Todd S. Laughlin, Michael W. Becker, Jane L. Liesveld, Deborah A

Alternative Splicing of a Novel Glycophorin Allele GPHe(GL) Generates Two Protein Isoforms in the Human Erythrocyte Membrane by Cheng-Han Huang, Olga O.

DNA-based prenatal exclusion of harlequin ichthyosis

by Cheng-Han Huang, Ying Chen, Marion E. Reid, and Christine Seidl

Volume 69, Issue 1, Pages (January 2006)

Yanggu Shi, Sharon F. Terry, Patrick F. Terry, Lionel G

Herlitz Junctional Epidermolysis Bullosa: Novel and Recurrent Mutations in the LAMB3 Gene and the Population Carrier Frequency Aoi Nakano, Ellen Pfendner,

Mutations in the Liver Glycogen Phosphorylase Gene (PYGL) Underlying Glycogenosis Type VI (Hers Disease) Barbara Burwinkel, Henk D. Bakker, Eliezer Herschkovitz,

Quantitative Analysis of Survival Motor Neuron Copies: Identification of Subtle SMN1 Mutations in Patients with Spinal Muscular Atrophy, Genotype-Phenotype.

Combination of a Novel Frameshift Mutation (1929delCA) and a Recurrent Nonsense Mutation (W610X) of the LAMB3 Gene in a Japanese Patient with Herlitz.

T. Ohta, K. Buiting, H. Kokkonen, S. McCandless, S. Heeger, H

Aoi Nakano, Hajime Nakano, Sal LaForgia, Leena Pulkkinen, Jouni Uitto

Autosomal-Recessive Congenital Cerebellar Ataxia Is Caused by Mutations in Metabotropic Glutamate Receptor 1 Velina Guergueltcheva, Dimitar N. Azmanov,

Volume 54, Issue 3, Pages (September 1998)

Investigation of the human stem cell factor KIT ligand gene, KITLG, in women with 46,XX spontaneous premature ovarian failure Emily S. Hui, B.A., Ekemini.

A Novel Syndrome Combining Thyroid and Neurological Abnormalities Is Associated with Mutations in a Monocarboxylate Transporter Gene Alexandra M. Dumitrescu,

Analysis of an exon 1 polymorphism of the B2 bradykinin receptor gene and its transcript in normal subjects and patients with C1 inhibitor deficiency

Epidermolysis Bullosa: Novel and De Novo Premature Termination Codon and Deletion Mutations in the Plectin Gene Predict Late-Onset Muscular Dystrophy

Volume 58, Issue 4, Pages (October 2000)

Double Heterozygosity for a RET Substitution Interfering with Splicing and an EDNRB Missense Mutation in Hirschsprung Disease Alberto Auricchio, Paola.

Molecular Characterization of WFS1 in Patients with Wolfram Syndrome

Analysis of Rare APC Variants at the mRNA Level

Peter Ianakiev, Michael W

Trans-Splicing to Spliceosomal U2 snRNA Suggests Disruption of Branch Site-U2 Pairing during Pre-mRNA Splicing Duncan J. Smith, Charles C. Query, Maria.

Novel SLC39A4 Mutations in Acrodermatitis Enteropathica

Structure of the GM2A Gene: Identification of an Exon 2 Nonsense Mutation and a Naturally Occurring Transcript with an In-Frame Deletion of Exon 2 Biao.

Comprehensive Mutation Analysis of the CYP21A2 Gene

Cycloheximide Facilitates the Identification of Aberrant Transcripts Resulting from a Novel Splice-Site Mutation in COL17A1 in a Patient with Generalized.

Laminin-5 Mutational Analysis in an Italian Cohort of Patients with Junctional Epidermolysis Bullosa Patrizia Posteraro, Naomi De Luca, Guerrino Meneguzzi,

Imprinting at the SMPD1 Locus: Implications for Acid Sphingomyelinase–Deficient Niemann-Pick Disease Calogera M. Simonaro, Jae-Ho Park, Efrat Eliyahu,

Volume 2, Issue 2, Pages (August 1998)

A Homozygous Nonsense Mutation in Type XVII Collagen Gene (COL17A1) Uncovers an Alternatively Spliced mRNA Accounting for an Unusually Mild Form of Non-Herlitz.

The γ-Crystallins and Human Cataracts: A Puzzle Made Clearer

Maternal Uniparental Meroisodisomy in the LAMB3 Region of Chromosome 1 Results in Lethal Junctional Epidermolysis Bullosa Yasuko Takizawa, Leena Pulkkinen,

Detection of the Activating JAK2 V617F Mutation in Paraffin-Embedded Trephine Bone Marrow Biopsies of Patients with Chronic Myeloproliferative Diseases

Deletion of the Cytoplasmatic Domain of BP180/Collagen XVII Causes a Phenotype with Predominant Features of Epidermolysis Bullosa Simplex Marcel Huber,

A Novel Point Mutation Affecting the Tyrosine Kinase Domain of the TRKA Gene in a Family with Congenital Insensitivity to Pain with Anhidrosis Shinichi.

Volume 64, Issue 5, Pages (November 2003)

Volume 54, Issue 1, Pages (July 1998)

Dominique J. Verlaan, Adrian M. Siegel, Guy A. Rouleau

Volume 58, Issue 2, Pages (August 2000)

Analysis of GNAS1 and Overlapping Transcripts Identifies the Parental Origin of Mutations in Patients with Sporadic Albright Hereditary Osteodystrophy.

Systematic Analysis of Molecular Defects in the Ferrochelatase Gene from Patients with Erythropoietic Protoporphyria U.B. Rüfenacht, L. Gouya, X. Schneider-Yin,

Opitz G/BBB Syndrome in Xp22: Mutations in the MID1 Gene Cluster in the Carboxy- Terminal Domain Karin Gaudenz, Erich Roessler, Nandita Quaderi, Brunella.

Ken-Ichi Egoshi, Koichiro Akakura, Takaomi Kodama, Haruo Ito

Volume 56, Issue 5, Pages (November 1999)

Masahide Yazaki, Sandra A. Farrell, Merrill D. Benson

Compound Heterozygosity for Novel Splice Site Mutations in the BPAG2/COL17A1 Gene Underlies Generalized Atrophic Benign Epidermolysis Bullosa Leena Pulkkinen,

Wook Lew Journal of Investigative Dermatology

Volume 55, Issue 1, Pages (January 1999)

Volume 57, Issue 6, Pages (June 2000)

Identification of Recurrent Mutations in the ARS (Component B) Gene Encoding SLURP-1 in Two Families with Mal de Meleda Kimberley Morine Ward, Jülide.

The 97 kDa Linear IgA Bullous Dermatosis Antigen is not Expressed in a Patient with Generalized Atrophic Benign Epidermolysis Bullosa with a Novel Homozygous.

Cystinuria subtype and the risk of nephrolithiasis1

Anthony M. Raizis, Martin M. Ferguson, David T. Nicholls, Derek W

Volume 57, Issue 1, Pages (January 2000)

Two Exon-Skipping Mutations as the Molecular Basis of Succinic Semialdehyde Dehydrogenase Deficiency (4-Hydroxybutyric Aciduria) Ken L. Chambliss, Debra.

Is Screening of the Candidate Gene Necessary in Unrelated Partners of Members of Families with Herlitz Junctional Epidermolysis Bullosa? Alfred Klausegger,

Structure of the IFL1 Gene and the Nature of the Mutations in the ifl1 Alleles.(A) A schematic representation of the exon and intron organization of the.

Mutation of the Ca2+ Channel β Subunit Gene Cchb4 Is Associated with Ataxia and Seizures in the Lethargic (lh) Mouse Daniel L Burgess, Julie M Jones,

Kit-Sing Au, Adelaide A. Hebert, E. Steve Roach, Hope Northrup

Quantitative Analysis of Survival Motor Neuron Copies: Identification of Subtle SMN1 Mutations in Patients with Spinal Muscular Atrophy, Genotype-Phenotype.

Richard J. Wenstrup, Jane B. Florer, Marcia C

Loss-of-Function Mutations in a Human Gene Related to Chlamydomonas reinhardtii Dynein IC78 Result in Primary Ciliary Dyskinesia Gaëlle Pennarun, Estelle.

Familial Porphyria Cutanea Tarda: Characterization of Seven Novel Uroporphyrinogen Decarboxylase Mutations and Frequency of Common Hemochromatosis Alleles

Exon Skipping in IVD RNA Processing in Isovaleric Acidemia Caused by Point Mutations in the Coding Region of the IVD Gene Jerry Vockley, Peter K. Rogan,

Identification of a New Splice Form of the EDA1 Gene Permits Detection of Nearly All X- Linked Hypohidrotic Ectodermal Dysplasia Mutations Alex W. Monreal,

Novel Mutations in the LAMB3 Gene Shared by Two Japanese Unrelated Families with Herlitz Junctional Epidermolysis Bullosa, and Their Application for Prenatal.

Identification of Novel pro-α2(IX) Collagen Gene Mutations in Two Families with Distinctive Oligo-Epiphyseal Forms of Multiple Epiphyseal Dysplasia Paul.

Presentation transcript:

SLC7A9 mutations in all three cystinuria subtypes Daniel Leclerc, Marylise Boutros, Daniel Suh, Qing Wu, Manuel Palacin, James R. Ellis, Paul Goodyer, Rima Rozen Kidney International Volume 62, Issue 5, Pages 1550-1559 (November 2002) DOI: 10.1046/j.1523-1755.2002.00602.x Copyright © 2002 International Society of Nephrology Terms and Conditions

Figure 1 DNA diagnostic tests for mutations inSLC7A9. Fragments were amplified using primers indicated in Table 2, digested with appropriate restriction enzymes (except in A) and analyzed by acrylamide gel electrophoresis. The letter C above the lanes stands for controls. The asterisks indicate bands that are specific for the mutated alleles. Image E is an autoradiogram. All other gels were stained with ethidium bromide. (A) Detection of heteroduplexes caused by IVS12+4delAGTA in segment XI for two members of family 1940. (B) SexAI digestion of proband AW (872-01) and two controls for the 1491G→T mutation (E436X). Only the mutant PCR fragment contains a SexAI site that cleaves the fragment of 370bp into 195bp and 175bp fragments. (C) NlaIII digestion of segment IX for AW (872-01) and three controls. The presence of mutation IVS9-17G→A is shown by bands of 62bp and 48bp. (D) DdeI digestion of probands DR (918-01), PD (1390-01) and two controls for the 799insA mutation. The mutation obliterates a DdeI site encompassing the 3′end of the modified PCR primer. DdeI normally cleaves twice in the 177bp product, generating bands of 104, 54 and 19bp (the 19bp fragment is not seen on this gel). In the absence of one of these restriction sites, a fragment of 124bp (that contains an extra base) is seen in probands. (E) MnlI restriction analysis of a 225bp PCR product. The mutation 967C→T (P261L) results in the creation of an extra MnlI site in the amplicon, visible as a 40bp band specific to the mutant allele. (F) SduI digestion of proband MS (1245-03) and two controls for diagnostic of the 967C→T (P261L) mutation. Only the control PCR fragments results in an artificially-created SduI site, making the 123bp segment specific for the mutant allele. (G) AciI restriction analysis of segment IX PCR products. The 1245G→A (A354T) mutation abolishes one of the four AciI restriction sites in the PCR product of patient CL (988-01). (H) Diagnostic for the 316T→C (I44T) mutation found in DH (1898-03). The mutation results in the creation of a second TspRI site in the 238bp fragment II. Kidney International 2002 62, 1550-1559DOI: (10.1046/j.1523-1755.2002.00602.x) Copyright © 2002 International Society of Nephrology Terms and Conditions

Figure 2 Deletion of fourbp in patient CH (1940-02). (A) Sequence surrounding the mutated site. The vertical bar shows the exon 12/intron 12 junction. The two boxes show the direct repeat of four bases. (B) Comparison of the normal and mutant sequences to the consensus donor site. The optimal donor site sequence was deduced from 3724 compiled 5′ splice sites19. The nucleotide frequencies observed by Senapathy et al19 at each position are shown under the sequences as a percentage. (C) Donor site evaluation for normal and mutant sequences, based on Neural Network analysis method18 or information theory model15. Splice sites sequences are shown by sequence walkers, in which the height of each letter is the contribution of that base to the total information of the site (in bits)16. The upper boundary of the vertical rectangles is at +2 bits, and the lower boundary is at -3 bits. Letters that are upside down represent negative contributions. The top walker diagram depicts the natural splice site and the lower one corresponds to the mutated sequence. The deletion substantially lowers the Ri value of the donor site, making it non-functional17. Kidney International 2002 62, 1550-1559DOI: (10.1046/j.1523-1755.2002.00602.x) Copyright © 2002 International Society of Nephrology Terms and Conditions

Figure 3 Context associated with mutation IVS9-17G→A. The G→A change is shown at position -17, between the 3′ splice junction and the potential branchpoint sequence20. Kidney International 2002 62, 1550-1559DOI: (10.1046/j.1523-1755.2002.00602.x) Copyright © 2002 International Society of Nephrology Terms and Conditions

Figure 4 Pedigree andSLC7A9 subtypes for family 1245. Fully-blackened symbols denote dominant cystinuria. Dotted boxes contain urinary cystine level (μmol cystine/g creatinine), type of cystinuria and SLC7A9 mutations. The maternal grandfather was a severe cystinuria case with stones. Because DNA was not available for the grandfather, the mutation shown (799insA/N) is predicted from data obtained from the proband and his mother. Kidney International 2002 62, 1550-1559DOI: (10.1046/j.1523-1755.2002.00602.x) Copyright © 2002 International Society of Nephrology Terms and Conditions