Maspardin Is Mutated in Mast Syndrome, a Complicated Form of Hereditary Spastic Paraplegia Associated with Dementia Michael A. Simpson, Harold Cross,

Slides:

Advertisements

Similar presentations

A New Locus for Autosomal Recessive Hereditary Spastic Paraplegia Maps to Chromosome 16q24.3 Giuseppe De Michele, Maurizio De Fusco, Francesca Cavalcanti,

Advertisements

Homozygous Defects in LMNA, Encoding Lamin A/C Nuclear-Envelope Proteins, Cause Autosomal Recessive Axonal Neuropathy in Human (Charcot-Marie-Tooth Disorder.

Homozygosity Mapping in Families with Joubert Syndrome Identifies a Locus on Chromosome 9q34.3 and Evidence for Genetic Heterogeneity Kathrin Saar, Lihadh.

A Homozygous Missense Mutation in TGM5 Abolishes Epidermal Transglutaminase 5 Activity and Causes Acral Peeling Skin Syndrome Andrew J. Cassidy, Maurice.

Strong Evidence That KIAA0319 on Chromosome 6p Is a Susceptibility Gene for Developmental Dyslexia Natalie Cope, Denise Harold, Gary Hill, Valentina.

A Mutation in the Vesicle-Trafficking Protein VAPB Causes Late-Onset Spinal Muscular Atrophy and Amyotrophic Lateral Sclerosis Agnes L. Nishimura, Miguel.

Mutations in FLVCR2 Are Associated with Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome (Fowler Syndrome) Esther Meyer, Christopher.

PLA2G6 Mutation Underlies Infantile Neuroaxonal Dystrophy

Genomewide Linkage Scan Identifies a Novel Susceptibility Locus for Restless Legs Syndrome on Chromosome 9p Shenghan Chen, William G. Ondo, Shaoqi Rao,

Mutations in TPRN Cause a Progressive Form of Autosomal-Recessive Nonsyndromic Hearing Loss Yun Li, Esther Pohl, Redouane Boulouiz, Margit Schraders,

Cohen Syndrome Is Caused by Mutations in a Novel Gene, COH1, Encoding a Transmembrane Protein with a Presumed Role in Vesicle-Mediated Sorting and Intracellular.

The SPCH1 Region on Human 7q31: Genomic Characterization of the Critical Interval and Localization of Translocations Associated with Speech and Language.

De Novo Loss-of-Function Mutations in SETD5, Encoding a Methyltransferase in a 3p25 Microdeletion Syndrome Critical Region, Cause Intellectual Disability

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

Factor H Mutations in Hemolytic Uremic Syndrome Cluster in Exons 18–20, a Domain Important for Host Cell Recognition Anna Richards, Mark R. Buddles,

Emma L. Baple, Reza Maroofian, Barry A. Chioza, Maryam Izadi, Harold E

A Homozygous Mutation in the Tight-Junction Protein JAM3 Causes Hemorrhagic Destruction of the Brain, Subependymal Calcification, and Congenital Cataracts

The American Journal of Human Genetics

Mutations in a Novel Gene with Transmembrane Domains Underlie Usher Syndrome Type 3 Tarja Joensuu, Riikka Hämäläinen, Bo Yuan, Cheryl Johnson, Saara.

A Gene Mutated in Nephronophthisis and Retinitis Pigmentosa Encodes a Novel Protein, Nephroretinin, Conserved in Evolution Edgar Otto, Julia Hoefele,

A Truncating Mutation of TRAPPC9 Is Associated with Autosomal-Recessive Intellectual Disability and Postnatal Microcephaly Ganeshwaran H. Mochida, Muhammad.

Evidence for a Nonallelic Heterogeneity of Epidermodysplasia Verruciformis with Two Susceptibility Loci Mapped to Chromosome Regions 2p21–p24 and 17q25

A Second Gene for Autosomal Dominant Möbius Syndrome Is Localized to Chromosome 10q, in a Dutch Family H.T.F.M. Verzijl, B. van den Helm, B. Veldman,

A Mutation in the Fibroblast Growth Factor 14 Gene Is Associated with Autosomal Dominant Cerebral Ataxia John C. van Swieten, Esther Brusse, Bianca M.

Refined Mapping of Naegeli–Franceschetti– Jadassohn Syndrome to a 6 cM Interval on Chromosome 17q11.2-q21 and Investigation of Candidate Genes Eli Sprecher,

Volume 119, Issue 2, Pages (August 2000)

Thomas C. Hart, Yingze Zhang, Michael C. Gorry, P

Mutations in ABCA12 Underlie the Severe Congenital Skin Disease Harlequin Ichthyosis P. David Kelsell, E. Elizabeth Norgett, Harriet Unsworth, Muy-Teck.

John D. Rioux, Valerie A. Stone, Mark J

Familial Juvenile Hyperuricemic Nephropathy: Localization of the Gene on Chromosome 16p11.2—and Evidence for Genetic Heterogeneity Blanka Stibůrková,

Airong Li, Sonia Davila, Laszlo Furu, Qi Qian, Xin Tian, Patrick S

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

Localization of a Gene for Benign Adult Familial Myoclonic Epilepsy to Chromosome 8q23.3-q24.1 Masaaki Mikami, Takeshi Yasuda, Akira Terao, Masayuki.

Mutations in FAM20C Are Associated with Lethal Osteosclerotic Bone Dysplasia (Raine Syndrome), Highlighting a Crucial Molecule in Bone Development M.A.

Mitochondrial Complex III Deficiency Associated with a Homozygous Mutation in UQCRQ Ortal Barel, Zamir Shorer, Hagit Flusser, Rivka Ofir, Ginat Narkis,

Genetic studies into inherited and sporadic hemolytic uremic syndrome

Disrupted in Schizophrenia 1 (DISC1): Association with Schizophrenia, Schizoaffective Disorder, and Bipolar Disorder Colin A. Hodgkinson, David Goldman,

Sadaf Naz, Chantal M. Giguere, David C. Kohrman, Kristina L

Autosomal-Dominant Woolly Hair Resulting from Disruption of Keratin 74 (KRT74), a Potential Determinant of Human Hair Texture Yutaka Shimomura, Muhammad.

A Novel 22q11.2 Microdeletion in DiGeorge Syndrome

Localization of a Gene for Duane Retraction Syndrome to Chromosome 2q31 Binoy Appukuttan, Elizabeth Gillanders, Suh-Hang Juo, Diana Freas-Lutz, Sandra.

Mutations in SCARF2 Are Responsible for Van Den Ende-Gupta Syndrome

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

Shwachman-Diamond Syndrome with Exocrine Pancreatic Dysfunction and Bone Marrow Failure Maps to the Centromeric Region of Chromosome 7 Sharan Goobie,

Identification of Mutations in TRAPPC9, which Encodes the NIK- and IKK-β-Binding Protein, in Nonsyndromic Autosomal-Recessive Mental Retardation Asif.

Evidence That the Penetrance of Mutations at the RP11 Locus Causing Dominant Retinitis Pigmentosa Is Influenced by a Gene Linked to the Homologous RP11.

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

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

Disruption of ERBB2IP Is not Associated with Dystrophic Epidermolysis Bullosa in Both Father and Son Carrying a Balanced 5;13 Translocation Margarita.

Mapping of Gene Loci for Nephronophthisis Type 4 and Senior-Løken Syndrome, to Chromosome 1p36 Maria J. Schuermann, Edgar Otto, Achim Becker, Katrin.

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,

Hereditary Isolated Renal Magnesium Loss Maps to Chromosome 11q23

Figure 1 Mutated CTSF in adult-onset neuronal ceroid lipofuscinosis and patients with frontotemporal dementia Mutated CTSF in adult-onset neuronal ceroid.

Mutations in the Gene Encoding Capillary Morphogenesis Protein 2 Cause Juvenile Hyaline Fibromatosis and Infantile Systemic Hyalinosis Sandra Hanks,

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

A Gene for an Autosomal Dominant Scleroatrophic Syndrome Predisposing to Skin Cancer (Huriez Syndrome) Maps to Chromosome 4q23 Young-Ae Lee, Howard P.

Simone Sanna-Cherchi, Gianluca Caridi, Patricia L

Alexandre Irrthum, Marika J

Assignment of the Muscle-Eye-Brain Disease Gene to 1p32-p34 by Linkage Analysis and Homozygosity Mapping Bru Cormand, Kristiina Avela, Helena Pihko,

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

Cohen Syndrome Is Caused by Mutations in a Novel Gene, COH1, Encoding a Transmembrane Protein with a Presumed Role in Vesicle-Mediated Sorting and Intracellular.

Homozygosity Mapping in Families with Joubert Syndrome Identifies a Locus on Chromosome 9q34.3 and Evidence for Genetic Heterogeneity Kathrin Saar, Lihadh.

Mutations in the Fatty Acid 2-Hydroxylase Gene Are Associated with Leukodystrophy with Spastic Paraparesis and Dystonia Simon Edvardson, Hiroko Hama,

Mutations in Two Nonhomologous Genes in a Head-to-Head Configuration Cause Ellis- van Creveld Syndrome Victor L. Ruiz-Perez, W.J. Stuart Tompson, J. Helen.

A Locus for Autosomal Dominant Hereditary Spastic Ataxia, SAX1,Maps to Chromosome 12p13 I.A. Meijer, C.K. Hand, K.K. Grewal, M.G. Stefanelli, E.J. Ives,

A Truncating Mutation of TRAPPC9 Is Associated with Autosomal-Recessive Intellectual Disability and Postnatal Microcephaly Ganeshwaran H. Mochida, Muhammad.

Glycyl tRNA Synthetase Mutations in Charcot-Marie-Tooth Disease Type 2D and Distal Spinal Muscular Atrophy Type V Anthony Antonellis, Rachel E. Ellsworth,

Mapping of a New SGBS Locus to Chromosome Xp22 in a Family with a Severe Form of Simpson-Golabi-Behmel Syndrome L.M. Brzustowicz, S. Farrell, M.B. Khan,

Autosomal Recessive Cerebellar Ataxia with Oculomotor Apraxia (Ataxia- Telangiectasia–Like Syndrome) Is Linked to Chromosome 9q34 Andrea H. Németh, Elena.

Presentation transcript:

Maspardin Is Mutated in Mast Syndrome, a Complicated Form of Hereditary Spastic Paraplegia Associated with Dementia Michael A. Simpson, Harold Cross, Christos Proukakis, Anna Pryde, Ruth Hershberger, Arnaud Chatonnet, Michael A. Patton, Andrew H. Crosby The American Journal of Human Genetics Volume 73, Issue 5, Pages 1147-1156 (November 2003) DOI: 10.1086/379522 Copyright © 2003 The American Society of Human Genetics Terms and Conditions

Figure 1 MRI of patient 17, showing thin corpus callosum and cerebral atrophy (A) and periventricular white-matter hyperintensity (B) The American Journal of Human Genetics 2003 73, 1147-1156DOI: (10.1086/379522) Copyright © 2003 The American Society of Human Genetics Terms and Conditions

Figure 2 Pedigree of the large Amish family with Mast syndrome, with consanguinity dating to the 17th century, showing haplotypes for markers across the SPG21 interval The American Journal of Human Genetics 2003 73, 1147-1156DOI: (10.1086/379522) Copyright © 2003 The American Society of Human Genetics Terms and Conditions

Figure 3 Multipoint LOD scores for markers situated across the SPG21 locus, flanked by markers D15S108 and D15S1507, producing a peak score of 15.1 for marker repeat 3. The American Journal of Human Genetics 2003 73, 1147-1156DOI: (10.1086/379522) Copyright © 2003 The American Society of Human Genetics Terms and Conditions

Figure 4 A schematic transcript map of the SPG21 locus, located within contig NT_010265 and spanning BAC clones AC069368, AC013691, and AC013553 (NCBI). The relative positions of the markers used for haplotyping, transcripts (and direction of transcription) located within and around the critical region, and the 601insA mutation in ACP33 are shown. The American Journal of Human Genetics 2003 73, 1147-1156DOI: (10.1086/379522) Copyright © 2003 The American Society of Human Genetics Terms and Conditions

Figure 5 Sequence chromatograms of the region around the exon 7 601insA mutation (arrow) of ACP33 in a wild-type homozygote (A), a homozygous affected individual (B), and a carrier parent (C). The American Journal of Human Genetics 2003 73, 1147-1156DOI: (10.1086/379522) Copyright © 2003 The American Society of Human Genetics Terms and Conditions

Figure 6 Alignment of maspardin with pseudomonas fluorescens chloroperoxidase (SwissProt: O31158 PRXC_PSEFL, PDB:1A8S). Line 1 shows the predicted secondary structure (“C3” loop, “E” strand, and “H” helix); lines 2 and 3 show the sequence of maspardin and chloroperoxydase, respectively; line 4 shows the known secondary structure of PRXC_PSEFL; and line 5, CORE, is a measure of the burial and number of contacts made by each residue, on a scale between 0 (not buried/few contacts) and 9 (very buried/many contacts). Amino acids of the catalytic triad of PRXC_PSEFL are shown in bold and are marked by an asterisk (*). The American Journal of Human Genetics 2003 73, 1147-1156DOI: (10.1086/379522) Copyright © 2003 The American Society of Human Genetics Terms and Conditions

Figure 7 Model of the structure of maspardin on the basis of the results of 3D-PSSM, with 1A8S as a template, which indicates that two of the three residues (Gln227 and Asn255) do not conform to the α/β hydrolase catalytic triad and that Asp226 is in the opposite orientation. Alpha helices are shown in yellow, and beta strands are shown in blue. The American Journal of Human Genetics 2003 73, 1147-1156DOI: (10.1086/379522) Copyright © 2003 The American Society of Human Genetics Terms and Conditions