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

Slides:

Advertisements

Similar presentations

Detection of Exon 12 Mutations in the JAK2 Gene

Advertisements

Mutation Spectrum of the Survival of Motor Neuron 1 and Functional Analysis of Variants in Chinese Spinal Muscular Atrophy Yu-jin Qu, Jin-li Bai, Yan-yan.

Splicing defects in the CFTR gene: Minigene analysis of two mutations, G>C and A>G Gwendal Dujardin, Diane Commandeur, Catherine Le Jossic-Corcos,

Deficiency of the ADP-Forming Succinyl-CoA Synthase Activity Is Associated with Encephalomyopathy and Mitochondrial DNA Depletion Orly Elpeleg, Chaya.

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

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

Volume 89, Issue 5, Pages (May 1997)

The Molecular Basis of Malonyl-CoA Decarboxylase Deficiency

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

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 Alu-Like Element Rearranged in the Dystrophin Gene Causes a Splicing Mutation in a Family with X-Linked Dilated Cardiomyopathy Alessandra Ferlini,

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

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

Volume 54, Issue 3, Pages (September 1998)

Detection of Exon 12 Mutations in the JAK2 Gene

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

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

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

Novel SLC39A4 Mutations in Acrodermatitis Enteropathica

Variation in the Vitreous Phenotype of Stickler Syndrome Can Be Caused by Different Amino Acid Substitutions in the X Position of the Type II Collagen.

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.

Volume 119, Issue 2, Pages (August 2000)

Survival of Male Patients with Incontinentia Pigmenti Carrying a Lethal Mutation Can Be Explained by Somatic Mosaicism or Klinefelter Syndrome The.

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

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,

Laurent Gouya Journal of Investigative Dermatology

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.

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

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

A Recurrent Mutation in the ARS (Component B) Gene Encoding SLURP-1 in Turkish Families with Mal de Meleda: Evidence of a Founder Effect Guofang Hu,

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.

A Mutation in the Variable Repeat Region of the Aggrecan Gene (AGC1) Causes a Form of Spondyloepiphyseal Dysplasia Associated with Severe, Premature.

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.

A Recurrent RNA-Splicing Mutation in the SEDL Gene Causes X-Linked Spondyloepiphyseal Dysplasia Tarda George E. Tiller, Vickie L. Hannig, Damon Dozier,

Ryan McDaniell, Daniel M. Warthen, Pedro A

A Novel Arginine→Serine Mutation in EDA1 in a Japanese Family with X-Linked Anhidrotic Ectodermal Dysplasia Noriaki Aoki, Kaoru Ito, Toshiaki Tachibana,

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.

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

SLC7A9 mutations in all three cystinuria subtypes

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,

Mutation Analysis of the Entire PKD1 Gene: Genetic and Diagnostic Implications Sandro Rossetti, Lana Strmecki, Vicki Gamble, Sarah Burton, Vicky Sneddon,

Wook Lew Journal of Investigative Dermatology

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

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.

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

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

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

Mutations in CHEK2 Associated with Prostate Cancer Risk

Bart A. Jessen, Marjorie A. Phillips, Robert H. Rice

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.

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

Hermansky-Pudlak Syndrome Type 3 in Ashkenazi Jews and Other Non–Puerto Rican Patients with Hypopigmentation and Platelet Storage-Pool Deficiency Marjan.

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,

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

Presentation transcript:

Identification of Novel pro-α2(IX) Collagen Gene Mutations in Two Families with Distinctive Oligo-Epiphyseal Forms of Multiple Epiphyseal Dysplasia Paul Holden, Elizabeth G. Canty, Geert R. Mortier, Bernhard Zabel, Jurgen Spranger, Andrew Carr, Michael E. Grant, John A. Loughlin, Michael D. Briggs The American Journal of Human Genetics Volume 65, Issue 1, Pages 31-38 (July 1999) DOI: 10.1086/302440 Copyright © 1999 The American Society of Human Genetics Terms and Conditions

Figure 1 Pedigrees of two families with MED and COL9A2 mutations. a, Family K. b, Family G. In both families, an arrow indicates the proband. The American Journal of Human Genetics 1999 65, 31-38DOI: (10.1086/302440) Copyright © 1999 The American Society of Human Genetics Terms and Conditions

Figure 2 Radiographic findings in individual JK and affected individuals from family G. a, Individual JK at age 15 years. b, Individual JK at age 9 years 9 mo. Note flattened and irregular epiphyses. c, Individual JK at age 11 years 5 mo. d, Individual IV-2 (family G) at age 14 years 6 mo. Note flattened irregular epiphyses and metal plates from the tibial osteotomy that was performed at age 13 years. e, Individual IV-1 (family G) at age 10 years. The American Journal of Human Genetics 1999 65, 31-38DOI: (10.1086/302440) Copyright © 1999 The American Society of Human Genetics Terms and Conditions

Figure 3 COL9A2 splice-site mutation in family K. a, Nucleotide sequence of exon 3 (upper case) /intron 3 (lower case) boundary. Shown at the top is the wild-type sequence; shown below is the sequence from the mutant allele. Indicated by an arrow is the G→A transition at the last nucleotide of exon 3. b, PAGE analysis of COL9A2 exon3/intron3 genomic DNA fragment containing the mutation. The mutation disrupts a HphI restriction-endonuclease site (indicated by an asterisk [*]). JK and his affected mother, UK, who are heterozygous for the mutation, show both digested and undigested product, whereas a control sample (lane C) shows only the digested product. The American Journal of Human Genetics 1999 65, 31-38DOI: (10.1086/302440) Copyright © 1999 The American Society of Human Genetics Terms and Conditions

Figure 4 COL9A2 splice-site mutation in family G. a, Nucleotide sequence of exon 3 (upper case) /intron 3 (lower case) boundary. Shown at the top is the wild-type sequence; shown below is the sequence from the mutant allele. Indicated by an arrow is the G→C transversion at position +5 of intron 3. b, PAGE analysis of COL9A2 exon3/intron3 genomic fragment containing the mutation. The mutation creates a MaeIII restriction-endonuclease site (indicated by an asterisk [*]). Affected individuals of family G, who are heterozygous for the mutation, show both undigested and digested product; a control sample (lane C) shows only the undigested product. The American Journal of Human Genetics 1999 65, 31-38DOI: (10.1086/302440) Copyright © 1999 The American Society of Human Genetics Terms and Conditions

Figure 5 6% PAGE analysis of PCR-amplified COL9A2 cDNA from a control sample (lane C) and from patients MG and JK. The control shows the expected DNA fragment of 196 bp, whereas both patient samples show both normal and shortened DNA fragments. The white arrow indicates putative heteroduplex molecules, formed between normal and deleted DNA fragments. The American Journal of Human Genetics 1999 65, 31-38DOI: (10.1086/302440) Copyright © 1999 The American Society of Human Genetics Terms and Conditions

Figure 6 BpmI restriction-enzyme digestion of COL9A2 cDNA. a, Possible combinations of COL9A2 mRNA transcripts. At the top is the normal transcript with exons 2–5 (partial) and G as the last nucleotide of exon 3 (boxed). In the middle is a normal-sized transcript (exons 2–5) but with A as the last nucleotide of exon 3 (boxed). Also enclosed in a box is the recognition sequence of BpmI. At the bottom is the incorrectly spliced transcript showing the loss of exon 3. b, 6% PAGE analysis of COL9A2 cDNA amplified by PCR from a control sample (lane C) and patient JK, before (−) and after (+) digestion with BpmI. The American Journal of Human Genetics 1999 65, 31-38DOI: (10.1086/302440) Copyright © 1999 The American Society of Human Genetics Terms and Conditions