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.

Slides:

Advertisements

Similar presentations

Genetics of Stickler Syndrome

Advertisements

Diagnostic Testing for Rett Syndrome by DHPLC and Direct Sequencing Analysis of the MECP2 Gene: Identification of Several Novel Mutations and Polymorphisms

Screening for Mutations in Kidney-Related Genes Using SURVEYOR Nuclease for Cleavage at Heteroduplex Mismatches Konstantinos Voskarides, Constantinos.

A Common Genetic Polymorphism (46 C to T Substitution) in the 5′-Untranslated Region of the Coagulation Factor XII Gene Is Associated With Low Translation.

Jacek Majewski The American Journal of Human Genetics

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

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

William A. Paznekas, Michael L. Cunningham, Timothy D. Howard, Bruce R

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

Molecular Mechanisms of Junctional Epidermolysis Bullosa: Col15 Domain Mutations Decrease the Thermal Stability of Collagen XVII Laura Väisänen, Cristina.

Genomic Amplification of the Human Plakophilin 1 Gene and Detection of a New Mutation in Ectodermal Dysplasia/Skin Fragility Syndrome Neil V. Whittock,

A Comparative Study of Fibrous Dysplasia and Osteofibrous Dysplasia with Regard to GSα Mutation at the Arg201 Codon Akio Sakamoto, Yoshinao Oda, Yukihide.

A Defect in the TUSC3 Gene Is Associated with Autosomal Recessive Mental Retardation Masoud Garshasbi, Valeh Hadavi, Haleh Habibi, Kimia Kahrizi, Roxana.

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

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,

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

Peter Ianakiev, Michael W

A Synonymous Mutation in the CFTR Gene Causes Aberrant Splicing in an Italian Patient Affected by a Mild Form of Cystic Fibrosis Valeria Faa′, Alessandra.

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.

Volume 119, Issue 2, Pages (August 2000)

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

Homozygous and heterozygous Arg614Cys mutations (1840C→T) in the ryanodine receptor gene co-segregate with malignant hyperthermia susceptibility in a.

Mutation Analysis of SLC26A4 for Pendred Syndrome and Nonsyndromic Hearing Loss by High-Resolution Melting Neng Chen, Lisbeth Tranebjærg, Nanna Dahl.

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

Mental Retardation and Abnormal Skeletal Development (Dyggve-Melchior-Clausen Dysplasia) Due to Mutations in a Novel, Evolutionarily Conserved Gene Daniel.

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

Michaela Floeth, Leena Bruckner-Tuderman

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

Mutation of Solute Carrier SLC16A12 Associates with a Syndrome Combining Juvenile Cataract with Microcornea and Renal Glucosuria Barbara Kloeckener-Gruissem,

The role of sequence variations within the genes encoding collagen II, IX and XI in nonsyndromic, early-onset osteoarthritis E. Jakkula, M.D., M. Melkoniemi,

A Missense Mutation in the Zinc-Finger Domain of the Human Hairless Gene Underlies Congenital Atrichia in a Family of Irish Travellers Wasim Ahmad, Alan.

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

Mutations of the Ephrin-B1 Gene Cause Craniofrontonasal Syndrome

Distinct Mutations in the Receptor Tyrosine Kinase Gene ROR2 Cause Brachydactyly Type B Georg C. Schwabe, Sigrid Tinschert, Christian Buschow, Peter.

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

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.

Ryan McDaniell, Daniel M. Warthen, Pedro A

X-Linked Anhidrotic (Hypohidrotic) Ectodermal Dysplasia Caused by a Novel Mutation in EDA1 Gene: 406T>G (Leu55Arg) Francisco Martínez, José María Millán,

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

Richard A. King, Rebecca K. Willaert, Ramona M

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,

X-Linked Mental Retardation and Autism Are Associated with a Mutation in the NLGN4 Gene, a Member of the Neuroligin Family Frédéric Laumonnier, Frédérique.

Volume 58, Issue 2, Pages (August 2000)

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

Relationship between CFTR and CTRC Variants and the Clinical Phenotype in Late- Onset Cystic Fibrosis Disease with Chronic Pancreatitis Anna C. Tomaiuolo,

Compound Heterozygosity for a Recessive Glycine Substitution and a Splice Site Mutation in the COL7A1 Gene Causes an Unusually Mild Form of Localized.

Common Mutations in Arg304 of the p63 Gene in Ectrodactyly, Ectodermal Dysplasia, Clefting Syndrome: Lack of Genotype–Phenotype Correlation and Implications.

A Defect in the TUSC3 Gene Is Associated with Autosomal Recessive Mental Retardation Masoud Garshasbi, Valeh Hadavi, Haleh Habibi, Kimia Kahrizi, Roxana.

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,

Maple Syrup Urine Disease: Identification and Carrier-Frequency Determination of a Novel Founder Mutation in the Ashkenazi Jewish Population Lisa Edelmann,

A Unique Point Mutation in the PMP22 Gene Is Associated with Charcot-Marie-Tooth Disease and Deafness Margaret J. Kovach, Jing-Ping Lin, Simeon Boyadjiev,

Bruce L. Zuraw, MD, Jack Herschbach, BA

Mental Retardation and Abnormal Skeletal Development (Dyggve-Melchior-Clausen Dysplasia) Due to Mutations in a Novel, Evolutionarily Conserved Gene Daniel.

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

Early Onset of Severe Familial Amyotrophic Lateral Sclerosis with a SOD-1 Mutation: Potential Impact of CNTF as a Candidate Modifier Gene Ralf Giess,

Ataxia-Telangiectasia: Identification and Detection of Founder-Effect Mutations in the ATM Gene in Ethnic Populations Milhan Telatar, Sharon Teraoka,

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,

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

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

Marshall Syndrome Associated with a Splicing Defect at the COL11A1 Locus Andrew J. Griffith, Leslie K. Sprunger, D. Alexa Sirko-Osadsa, George E. Tiller,

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,

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

Presentation transcript:

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 Gly-X-Y Triple Helix Allan J. Richards, David M. Baguley, John R.W. Yates, Carol Lane, Mary Nicol, Peter S. Harper, John D. Scott, Martin P. Snead The American Journal of Human Genetics Volume 67, Issue 5, Pages 1083-1094 (November 2000) DOI: 10.1016/S0002-9297(07)62938-3 Copyright © 2000 The American Society of Human Genetics Terms and Conditions

Figure 1 Clinical phenotypes. A–C, MS12, age 17 years, showing mild nasal-root hypolasia and moderate midfacial hypoplasia and slender digits. D–F, MS16, age 14 years. Note anteverted nares and nasal-root hyoplasia and joint laxity. G–I, III-7, MS25, age 29 years. Note well-developed nasal bridge and root, moderate midfacial hypoplasia, and slender digits. The American Journal of Human Genetics 2000 67, 1083-1094DOI: (10.1016/S0002-9297(07)62938-3) Copyright © 2000 The American Society of Human Genetics Terms and Conditions

Figure 2 Vitreous phenotypes in Stickler syndrome. A, Membranous congenital vitreous anomaly seen in MS12 and MS16. Note vestigial gel occupying retrolental space and bordered by a distinct folded membrane (arrows). B, Beaded congenital vitreous anomaly: COL11A1 mutation (see Martin et al. 1999). Note irregularly thickened fiber bundles, giving a string-of-pearls appearance (arrows). C, Afibrillar congenital vitreous anomaly seen in MS25. Note complete absence of visible fiber bundles. D, Normal vitreous appearance. Note healthy compact homogenous fibrillar array. The American Journal of Human Genetics 2000 67, 1083-1094DOI: (10.1016/S0002-9297(07)62938-3) Copyright © 2000 The American Society of Human Genetics Terms and Conditions

Figure 3 COL2A1 genomic sequencing. The heterozygous (arrows) mutation-containing sequences obtained from affected individuals in MS12, MS16, and MS25 are shown under the normal sequence (N). Intron sequences are in lowercase, and coding sequences are in uppercase. The American Journal of Human Genetics 2000 67, 1083-1094DOI: (10.1016/S0002-9297(07)62938-3) Copyright © 2000 The American Society of Human Genetics Terms and Conditions

Figure 4 DNA analysis of families. A, DNA containing exon 26, which was amplified from MS16 (1) and MS12 (2–5) and digested with BbvI. Extra bands in samples from affected individuals, visualized after electrophoresis, are marked with arrows. Undigested DNA (lane U) and standard size markers (bp) were included on the gel. B, Results of [33P]dideoxynucleotide sequencing reaction, which was used to detect the mutation in MS25. Samples correspond to the pedigree shown above the gel. Family members not included in the analysis are situated on either side of the gel. Nucleotide numbers correspond to the complete COL2A1 gene sequence (Genome Database accession number L10347). The American Journal of Human Genetics 2000 67, 1083-1094DOI: (10.1016/S0002-9297(07)62938-3) Copyright © 2000 The American Society of Human Genetics Terms and Conditions

Figure 5 COL2A1 cDNA sequencing. Sequencing of cDNA amplified from an individual (MS20 C) with a nonsense mutation in exon 42 showed loss of heterozygosity when compared with the genomic sequence (MS20 G). Amplified cDNA from MS16 and MS25 showed heterozygosity for the mutations seen in genomic DNA (fig. 1). The American Journal of Human Genetics 2000 67, 1083-1094DOI: (10.1016/S0002-9297(07)62938-3) Copyright © 2000 The American Society of Human Genetics Terms and Conditions

Figure 6 Position of Arg→Cys substitutions in fibrillar collagens. The position of cysteine substitutions in the α1(I), α1(II), and α2(XI) collagens are illustrated. X-position changes are indicated below the line representing each molecule, whereas Y-position changes are indicated above the lines. Numbers represent the amino acid position within the helix. The resulting phenotypes are osteoarthritis (OA), spondyloepipheseal dysplasia (SED), SED congenita (SEDC), Stickler syndrome (SS), mild chondrodysplasia (MC), Stickler-like syndrome (SLS), classical Ehlers-Danlos syndrome (CEDS), and nonsyndromic deafness (DFN). The American Journal of Human Genetics 2000 67, 1083-1094DOI: (10.1016/S0002-9297(07)62938-3) Copyright © 2000 The American Society of Human Genetics Terms and Conditions