Mutations in Fibroblast Growth-Factor Receptor 3 in Sporadic Cases of Achondroplasia Occur Exclusively on the Paternally Derived Chromosome Douglas J.

Slides:

Advertisements

Similar presentations

Molecular Approaches for Screening of Genetic Diseases

Advertisements

Molecular Diagnostics in Preimplantation Genetic Diagnosis

DNA-based prenatal exclusion of harlequin ichthyosis

A Pseudo-Full Mutation Identified in Fragile X Assay Reveals a Novel Base Change Abolishing an EcoRI Restriction Site Shujian Liang, Harold N. Bass,

Suppression of Wild-Type Amplification by Selectivity Enhancing Agents in PCR Assays that Utilize SuperSelective Primers for the Detection of Rare Somatic.

Discordance between Genetic and Epigenetic Defects in Pseudohypoparathyroidism Type 1b Revealed by Inconsistent Loss of Maternal Imprinting at GNAS1

Philippe Szankasi, Mohamed Jama, David W. Bahler

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

Volume 127, Issue 5, Pages (November 2004)

A Novel Targeted Approach for Noninvasive Detection of Paternally Inherited Mutations in Maternal Plasma Jessica M.E. van den Oever, Ivonne J.H.M. van.

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

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

Volume 88, Issue 4, Pages (February 1997)

A novel mutation of HFE explains the classical phenotype of genetic hemochromatosis in a C282Y heterozygote Daniel F. Wallace, James S. Dooley, Ann P.

A Novel Skeletal Dysplasia with Developmental Delay and Acanthosis Nigricans Is Caused by a Lys650Met Mutation in the Fibroblast Growth Factor Receptor.

Evaluation of Parental Mitochondrial Inheritance in Neonates Born after Intracytoplasmic Sperm Injection Claude Danan, Damien Sternberg, André Van Steirteghem,

ATLAS: A System to Selectively Identify Human-Specific L1 Insertions

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

De Novo BRCA1 Mutation in a Patient with Breast Cancer and an Inherited BRCA2 Mutation Andrea Tesoriero, Chris Andersen, Melissa Southey, Gino Somers,

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

Analysis of Rare APC Variants at the mRNA Level

A Recurrent Intragenic Deletion in the Desmoglein 4 Gene Underlies Localized Autosomal Recessive Hypotrichosis Celia Moss, Amalia Martinez-Mir, HaMut.

Peter Ianakiev, Michael W

A Multi-Site Study for Detection of the Factor V (Leiden) Mutation from Genomic DNA Using a Homogeneous Invader Microtiter Plate Fluorescence Resonance.

Splice Site and Deletion Mutations in Keratin (KRT1 and KRT10) Genes: Unusual Phenotypic Alterations in Scandinavian Patients with Epidermolytic Hyperkeratosis

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.

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

Syed Hussain Askree, Lawrence N

Molecular Diagnostics in Preimplantation Genetic Diagnosis

Haploinsufficiency for One COL3A1 Allele of Type III Procollagen Results in a Phenotype Similar to the Vascular Form of Ehlers-Danlos Syndrome, Ehlers-Danlos.

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

Kimberly C. Sippel, Rebecca E. Fraioli, Gary D. Smith, Mary E

A Presenilin-1 Truncating Mutation Is Present in Two Cases with Autopsy-Confirmed Early-Onset Alzheimer Disease Carolyn Tysoe, Joanne Whittaker, John.

Philippe Burlet, Ph. D. , Nelly Frydman, D. Pharm. , Nadine Gigarel, B

DPY19L2 Deletion as a Major Cause of Globozoospermia

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

A Recurrent Expansion of a Maternal Allele with 36 CAG Repeats Causes Huntington Disease in Two Sisters Franco Laccone, Wilhelm Christian The American.

Amplification Refractory Mutation System, a Highly Sensitive and Simple Polymerase Chain Reaction Assay, for the Detection of JAK2 V617F Mutation in Chronic.

Novel Polymorphism in the FMR1 Gene Resulting in a “Pseudodeletion” of FMR1 in a Commonly Used Fragile X Assay Thomas M. Daly, Arash Rafii, Rick A. Martin,

Null Alleles of the COL5A1 Gene of Type V Collagen Are a Cause of the Classical Forms of Ehlers-Danlos Syndrome (Types I and II) Ulrike Schwarze, Mary.

Volume 54, Issue 1, Pages (July 1998)

Rapid Polymerase Chain Reaction-Based Detection of Epidermal Growth Factor Receptor Gene Mutations in Lung Adenocarcinomas Qiulu Pan, William Pao, Marc.

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

Recurrence of Marfan Syndrome as a Result of Parental Germ-Line Mosaicism for an FBN1 Mutation Terhi Rantamäki, Ilkka Kaitila, Ann-Christine Syvänen,

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.

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

Imprinting of Human GRB10 and Its Mutations in Two Patients with Russell-Silver Syndrome Hiroshi Yoshihashi, Katsuhiro Maeyama, Rika Kosaki, Tsutomu.

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

Rapid Detection of Hotspot Mutations in Epidermal Growth Factor Receptor by Polymerase Chain Reaction Facilitates the Management of Non-small Cell Lung.

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

Identification of a Lethal Form of Epidermolysis Bullosa Simplex Associated with a Homozygous Genetic Mutation in Plectin Maryse Bonduelle, Linda De.

Truncating Mutations of MAGEL2, a Gene within the Prader-Willi Locus, Are Responsible for Severe Arthrogryposis Dan Mejlachowicz, Flora Nolent, Jérome.

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

Constitutional Mutations of the hSNF5/INI1 Gene Predispose to a Variety of Cancers Nicolas Sévenet, Eammon Sheridan, Daniel Amram, Pascale Schneider,

A Mutation in the V1 Domain of K16 is Responsible for Unilateral Palmoplantar Verrucous Nevus Alessandro Terrinoni, Vincenzo De Laurenzi, Eleonora Candi,

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

Arun Kumar, Satish C. Girimaji, Mahesh R. Duvvari, Susan H. Blanton

Gonosomal Mosaicism for a Nonsense Mutation (R1947X) in the NF1 Gene in Segmental Neurofibromatosis Type 1 Claudia Consoli, Celia Moss, Stuart Green,

Mutations in CHEK2 Associated with Prostate Cancer Risk

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,

Alexandre Irrthum, Marika J

Polymorphic X-Chromosome Inactivation of the Human TIMP1 Gene

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

Epigenetic Allele Silencing Unveils Recessive RYR1 Mutations in Core Myopathies Haiyan Zhou, Martin Brockington, Heinz Jungbluth, David Monk, Philip Stanier,

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

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,

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:

Mutations in Fibroblast Growth-Factor Receptor 3 in Sporadic Cases of Achondroplasia Occur Exclusively on the Paternally Derived Chromosome Douglas J. Wilkin, Jinny K. Szabo, Rhoda Cameron, Shirley Henderson, Gary A. Bellus, Michelle L. Mack, Ilkka Kaitila, John Loughlin, Arnold Munnich, Bryan Sykes, Jacky Bonaventure, Clair A. Francomano The American Journal of Human Genetics Volume 63, Issue 3, Pages 711-716 (September 1998) DOI: 10.1086/302000 Copyright © 1998 The American Society of Human Genetics Terms and Conditions

Figure 1 FGFR3 achondroplasia mutant and wild-type allele-specific oligonucleotide primers, designed to create a mismatch at the nucleotide adjacent to the 3′ nucleotide, with the 3′ nucleotide corresponding to FGFR3 nucleotide 1138, the base mutated in the common achondroplasia mutation analyzed in this study. The normal-allele PCR primers (1138wt-F and 1138wt-R) contained the wild-type nucleotide G (or C on the reverse primer) as the 3′ base, maximizing the mismatch with the mutant allele. The mutant-allele PCR primers (1138mut-F and 1138mut-R) contain the achondroplasia-mutation nucleotide A (or T on the reverse primer) as the 3′ base, maximizing the mismatch with the normal allele. The American Journal of Human Genetics 1998 63, 711-716DOI: (10.1086/302000) Copyright © 1998 The American Society of Human Genetics Terms and Conditions

Figure 2 PmlI (A) and PflMI (B) restriction digestion of allele-specific PCR products, as recommended by the manufacturer. The sizes of products of restriction digestion are shown. Analyses of four families are presented. Allele-specific PCR of genomic DNA was performed with either a normal-sequence (wt) oligonucleotide primer or an oligonucleotide primer specific for the common achondroplasia mutation (mut) (see fig. 1). The allele-specific primer used in the PCR reactions is depicted as wt or mut. Reactions using DNA from the probands are shown in lanes 2, 3, 6, and 7. PCR using genomic DNA from the affected child was performed with either a wt oligonucleotide primer or a mut primer. Parental DNAs are shown in lanes 1, 4, 5, and 8. PCR of parental genomic DNA was performed with a wt primer. In each case shown, the allele amplifying with the mut primer is inherited from the father. The American Journal of Human Genetics 1998 63, 711-716DOI: (10.1086/302000) Copyright © 1998 The American Society of Human Genetics Terms and Conditions

Figure 3 Potential paternal and maternal alleles. The PmlI polymorphism is used as an example. Allele-specific PCR was performed with the proband's genomic DNA, and digestion was performed with the appropriate restriction enzyme. If the proband was heterozygous for the polymorphism, the parental DNAs were analyzed. The possible parental alleles and the parent from whom the mutant allele would be inherited are shown. +/+ = Homozygosity for the polymorphic sequence, −/− = homozygosity for the normal sequence, and +/− = heterozygosity at the site. The American Journal of Human Genetics 1998 63, 711-716DOI: (10.1086/302000) Copyright © 1998 The American Society of Human Genetics Terms and Conditions

Figure 4 Analysis of 99 probands. A total of 21, 9, and 17 probands were heterozygous for the PmlI, PflMI, and poly(G) polymorphisms, respectively. From those heterozygous probands, respectively, 19, 6, and 15 parental alleles were informative for the determination of the parental origin of the achondroplasia allele. In all 40 informative families, the mutant allele was inherited from the father. The American Journal of Human Genetics 1998 63, 711-716DOI: (10.1086/302000) Copyright © 1998 The American Society of Human Genetics Terms and Conditions

Figure 5 Sequence analysis of FGFR3 intron 9 poly(G) polymorphism. Normal intron 9 sequence (A) contains a stretch of 11 consecutive guanosine residues, whereas the polymorphic sequence (B) has a G deletion in this sequence. The American Journal of Human Genetics 1998 63, 711-716DOI: (10.1086/302000) Copyright © 1998 The American Society of Human Genetics Terms and Conditions