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简介 链接http://www.biochemj.org/csb/default.htm Cell Signalling Biology This major contribution to the field of cell signalling by one of the world's leading experts, Professor Sir Michael Berridge (Cambridge) is now sponsored by the Biochemical Journal's Signal Knowledge Environment ensuring online access is freely available to all. Cell Signalling Biology provides researchers, teachers and students alike with an outstanding online resource describing the biology of cell signalling. New updates covering cytokines and their receptors; virus recognition; transcriptional co-regulators/co-activators/co-repressors; checkpoint signalling; DNA damage; neuron subtypes; hypothalamic regulation; tumour suppressors; tumour metastasis and inflammation and cancer; Alzheimer's disease are now included. "A fantastic resource for educators and researchers alike, and for anyone interested in the basics and details of cell signalling pathways. The diagrams are particularly useful as teaching tools, I highly recommend this to anyone engaged in signalling research". Alex Toker, Harvard Medical School, Boston. View testimonials Watch a special Biochemical Society Centenary interview with Sir Michael Berridge entitled - Eureka Moments: The key that unlocked calcium in which Professor Sir Michael Berridge talks to Professor Robin Irvine about his 'Eureka Moment' in calcium signalling and his passion for trying to find the solution to interesting problems. -------------------------------------------------------------------------------- Contents 1 Introduction The aim of this website is to describe cell signalling within its biological context. There has been an explosion in the characterization of signalling components and pathways. The next major challenge is to understand how cells exploit this large signalling toolkit to assemble the specific signalling pathways they require to communicate with each other. Introduction Overview of cell signalling mechanisms Communication through electrical signals Communication through chemical signals ON mechanisms Cell stimuli Cytokines Receptors Transducers and amplifiers Intracellular messengers Sensors and effectors OFF mechanisms Information transfer mechanisms Conformational-coupling mechanisms Post-translational modifications Protein methylation Sumoylation Ubiquitination Ubiquitin signalling system Protein degradation DNA methylation Desensitization of cell signalling Spatial and temporal aspects of cell signalling Signalsome References for Module 1 2 Cell signalling pathways Cells use a large number of clearly defined signalling pathways to regulate their activity. This module focusses on the ON mechanisms responsible for transmitting information into the cell. Synopsis Intracellular signalling pathways Cyclic AMP signalling pathway Cyclic AMP formation Adenylyl cyclase (AC) Cyclic AMP signalling effectors Protein kinase A (PKA) Exchange proteins activated by cyclic AMP (EPACs) Cyclic AMP signalling functions Cyclic AMP hydrolysis Cyclic AMP efflux GTP-binding proteins Heterotrimeric G proteins Monomeric G proteins Ca2+ signalling Basic mechanism of Ca2+ signalling Ca2+ signalling signalsome Ca2+ signalling modules Ca2+ ON reactions Ca2+-induced Ca2+ release (CICR) Ca2+ OFF reactions Ca2+ buffers Ca2+ signalling function Spatiotemporal aspects of Ca2+ signalling Cyclic ADP-ribose (cADPR) signalling cADPR working hypothesis cADPR generation and metabolism cADPR control of Ca2+ release cADPR and cell regulation Nicotinic acid–adenine dinucleotide phosphate (NAADP) signalling NAADP generation and metabolism NAADP control of Ca2+ release Phosphoinositide signalling Phosphoinositide metabolism Inositol lipid metabolism Inositol phosphate metabolism Inositol 1,4,5-trisphosphate (InsP3)/Ca2+ signalling cassette Phospholipase C (PLC) Diacylglycerol (DAG)/protein kinase C (PKC) signalling cassette Protein kinase C (PKC) Phosphoinositide lipid signalling molecules PtdIns4,5P2 signalling cassette PtdIns 3-kinase signalling Insulin receptor Multipurpose inositol polyphosphate signalling pathway Nitric oxide (NO)/cyclic GMP signalling pathway Cyclic GMP signalling pathway Reactive nitrogen species (RNS) signalling Redox signalling Reactive oxygen species (ROS) signalling Mitogen-activated protein kinase (MAPK) signalling Overview Mitogen-activated protein kinase (MAPK) signalling toolkit Extracellular-signal-regulated kinase (ERK) pathway c-Jun N-terminal kinase (JNK) pathway p38 pathway Mitogen-activated protein kinase (MAPK) signalling properties Nuclear factor κB (NF-κB) signalling pathway Nuclear factor κB (NF-κB) signalling toolkit Tumour necrosis factor α (TNFα) signalling pathway Toll receptor signalling pathway Phospholipase D (PLD) signalling pathway Phospholipase D (PLD) activation Phosphatidic acid (PA) action Phosphatidic acid (PA) metabolism Sphingomyelin signalling pathway Generation and function of ceramide and sphingosine 1-phosphate (S1P) Sphingosine 1-phosphate (S1P) Ceramide Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling pathway Janus kinase (JAK)/signal transducer and activator of transcription (STAT) structure Signal transducer and activator of transcription (STAT) activation cascade Suppressor of cytokine signalling proteins (SOCS) Janus kinase (JAK)/signal transducer and activator of transcription (STAT) function in growth and development Smad signalling pathway Smad signalling toolkit Domain structure of the Smad family Smad signalling mechanism Transforming growth factor β (TGF-β) receptor activation Smad activation of transcription Modulation of Smad signalling Transforming growth factor β (TGF-β) inhibition of cell proliferation Wnt signalling pathways Wnts Canonical Wnt/β-catenin pathway Wnt/planar cell polarity (PCP) pathway Wnt/Ca2+ signalling pathway Casein kinase I (CKI) Casein kinase II (CK2) Hedgehog signalling pathway Hedgehog signalling toolkit Hedgehog activation of transcription Hedgehog signalling functions Notch signalling pathway Modulation of Notch signalling Endoplasmic reticulum (ER) stress signalling Unfolded protein response (UPR) Endoplasmic reticulum (ER) overload response (EOR) Activation of apoptosis Metabolic messengers AMP signalling pathway Adenosine monophosphate (AMP) AMP-activated protein kinase (AMPK) Adenosine triphosphate (ATP) Bicarbonate (HCO3−  Fatty acids NAD signalling pathways Sterol sensing and cholesterol biosynthesis References for Module 2 3 Ion channels Ion channels have two main signalling functions: either they can generate second messengers or they can function as effectors by responding to such messengers. Synopsis Ca2+ entry channels Voltage-operated channels (VOCs) Voltage-operated channel (VOC) terminology and classification Voltage-operated channel (VOC) structure Voltage-operated channel (VOC)-associated subunits Voltage-operated channel (VOC) properties Voltage-operated channel (VOC) distribution and function CaV1 family of L-type channels CaV1.1 L-type channel Modulation of the CaV1.1 L-type channel CaV1.2 L-type channel CaV2 family of N-type, P/Q-type and R-type channels CaV3 family of T-type channels Agonist-operated channels (AOCs) Receptor-operated channels (ROCs) Cysteine-loop receptors Structure and function of nicotinic acetylcholine receptors (nAChRs) Glutamate receptors Second messenger-operated channels (SMOCs) Arachidonic acid-regulated Ca2+ (ARC) channel Store-operated channels (SOCs) Transient receptor potential (TRP) ion channel family Structural organization of the transient receptor potential (TRP) ion channel family Canonical transient receptor potential (TRPC) family Vanilloid transient receptor potential (TRPV) family Melastatin-related transient receptor potential (TRPM) family Mucolipin transient receptor potential (TRPML) family TRPML1 TRPA1 Temperature sensing Polycystins Mechanotransduction Mechanosensitive channels K+ channels Voltage-dependent K+ (Kv) channels K+ channel auxiliary subunits Inward rectifier K+ (Kir) channels Ca2+-sensitive K+ channels K+ channel structure Large-conductance (BK) channel opening Intermediate-conductance (IK) and small-conductance (SK) channel opening G protein-gated inwardly rectifying K+ (KG) channels ATP-sensitive K+ (KATP) channels Hyperpolarizing-activated cyclic nucleotide-gated (HCN) channels Chloride channels and transporters Ca2+-sensitive Cl− channels (CLCAs) CLC chloride channels and transporters ATP-binding cassette (ABC) transporters ABCA1 ABCA2 ABCA3 ABCA4 ABCB4 ABCC1 ABCC4 ABCC7 ABCD1 Cystic fibrosis transmembrane conductance regulator (CFTR) Cation-chloride cotransporters Na+-K+-2Cl− cotransporter 1 (NKCC1) Na+-K+-2Cl− cotransporter 2 (NKCC2) Na+-Cl− cotransporter (NCC) K+-Cl− cotransporter 1 (KCC1) K+-Cl− cotransporter 2 (KCC2) K+-Cl− cotransporter 3 (KCC3) K+-Cl− cotransporter 4 (KCC4) WNK protein kinase WNK1 WNK2 WNK3 WNK4 Cell volume regulation Aquaporins Ca2+ release channels Ryanodine receptors (RYRs) Inositol 1,4,5-trisphosphate receptors (InsP3Rs) Luminal regulation of Ca2+ release channels Junctophilin (JP) References for Module 3 4 Sensors and effectors Signalling pathways regulate cellular processes by acting through sensors to stimulate the downstream effectors that are responsible for controlling different cellular processes. Synopsis Sensors Ca2+ sensors Calmodulin (CaM) Troponin C (TnC) Neuronal Ca2+ sensor (NCS) proteins Ca2+-binding proteins (CaBPs) Annexins S100 proteins Synaptotagmins Effectors Ca2+ effectors Phosphorylase kinase Myosin light chain kinase (MLCK) Calcineurin (CaN) Exocytosis Exocytotic mechanisms Exocytotic/endocytotic cycle Kiss-and-run vesicle fusion Exocytosis triggered by Ca2+ entry through voltage-operated channels (VOCs) Exocytosis triggered by Ca2+ release from internal stores Exocytotic machinery Ca2+-dependent exocytosis Phagocytosis Phagosome maturation Gene transcription Transcription factors Transcriptional co-regulators Transcription factor classification Transcription factor activation mechanisms Gene silencing Ubiquitin signalling and gene transcription Developmentally regulated transcription factors Nuclear receptors Hepatocyte nuclear factor 4α (HNF4α) Internal signal-dependent transcription factors Cell-surface receptor-dependent transcription factors Activation of transcription by cytosolic signals APP intracellular domain (AICD) β-Catenin as a transcription factor Interferon-regulatory factors (IFRs) LBP1 family of transcription factors Signal transducers and activators of transcription (STATs) Notch intracellular domain (NICD) Nuclear factor of activated T cells (NFAT) Nuclear factor κB (NF-κB) Single-minded 1(Sim1) Smads Activation of transcription by nuclear signals Activation of transcription factors by regulating their expression Signalsome stability Ciliary beating Primary cilium Actin remodelling Wiskott–Aldrich syndrome protein (WASP) Wiskott–Aldrich syndrome protein (WASP) verprolin homologous (WAVE) Actin-related protein 2/3 complex (Arp2/3 complex) Ena/vasodilator-stimulated phosphoprotein (VASP) family References for Module 4 5 Off mechanisms Signalling pathways are composed of the ON mechanisms that generate internal signals and the OFF mechanisms that remove these signals as cells recover from stimulation. Synopsis Protein phosphatases Protein tyrosine phosphatases (PTPs) Protein serine/threonine phosphatases Phosphodiesterase (PDE) PDE1 PDE2 PDE3 PDE4 PDE5 PDE6 Ca2+ pumps and exchangers Pump classification Properties of Ca2+ pumps Organization and distribution of Ca2+ pumps Mitochondria Generation of ATP Mitochondrial Ca2+ uptake Mitochondrial Ca2+ release Endoplasmic reticulum (ER)/mitochondrial Ca2+ shuttle Mitochondrial permeability transition pore (MTP) Mitochondrial modulation of Ca2+ signals Ca2+ modulation of mitochondrial function Mitochondrial motility References for Module 5 6 Spatial and temporal aspects of signalling The function and efficiency of cell signalling pathways are very dependent on their organization both in space and time. With regard to spatial organization, signalling components are highly organized with respect to their cellular location and how they transmit information from one region of the cell to another. Synopsis Spatial organization of signalling pathways Signal transduction domains Scaffolding/targeting proteins Macromolecular signalling complexes Lipid rafts and caveolae Lipid composition of rafts and caveolae Caveolae structure Signalling function of caveolae Cadherins Classical cadherins Catenins Desmosomal cadherins Protocadherins Atypical cadherins Cell adhesion complexes Focal adhesion complex Focal adhesion actin attachment Focal adhesion integrin signalling Podosome Local and global aspects of signalling Elementary and global aspects of Ca2+ signalling Cyclic AMP microdomains Reactive oxygen species (ROS) microdomains Temporal aspects of signalling Cellular oscillators Brain rhythm Membrane oscillators Cytosolic oscillators References for Module 6 7 Cellular processes Signalling pathways use different messenger systems acting through specific sensors and effectors to control a great variety of cell types Synopsis Mammalian cell types Metabolic energy network Control of food intake and body weight Glial cells Astrocytes Astrocyte structure Spatial buffering of K+ by astrocytes Neuronal–astrocyte communication Astrocyte–neuronal communication Astrocyte excitability Astrocyte regulation of cerebral blood flow Satellite glial cells Microglia Endothelial cells Endothelial regulation of paracellular permeability Skeletal muscle Skeletal muscle structure Excitation–contraction (E-C) coupling in skeletal muscle Excitation–metabolism coupling in skeletal muscle Insulin control of skeletal muscle glycogen synthesis Cardiac cells Sinoatrial node pacemaker cells Ventricular cells Atrial cells Smooth muscle cells Smooth muscle cell structure Smooth muscle cell excitation–contraction coupling Smooth muscle Ca2+ signalling Smooth muscle Rho/Rho kinase signalling Smooth muscle cell relaxation Nitric oxide (NO)/cyclic GMP and smooth muscle relaxation Smooth muscle cell Ca2+ sparks Smooth muscle activation mechanisms Vas deferens Uterine smooth muscle cells Detrusor smooth muscle cell Ureter smooth muscle cell Airway smooth muscle cells Vascular smooth muscle cells Smooth muscle cell cytosolic oscillator Myogenic vasoconstriction Corpus cavernosum smooth muscle cells Gastrointestinal smooth muscle cells Urethral smooth muscle cells Interstitial cells of Cajal Phase wave Ca2+ homoeostasis Hormonal regulation of Ca2+ homoeostasis Ca2+ reabsorption by the intestine Bone Bone remodelling Osteoblasts Osteocytes Osteoclasts Bone cell coupling Chondrocytes Skin Epidermis Keratinocytes Dermis Hair follicle Arrector pilli muscle Sebaceous gland Sweat gland Melanocytes Alimentary canal Stomach X/A-like cell Parietal cell Small intestine Colon Kidney Blood Na+ regulation Blood pressure Kidney structure Juxtaglomerular apparatus (JGA) Urine formation Salivary gland Salivary gland structure Salivary gland control mechanisms Exocrine pancreatic acinar cells Acetylcholine-induced pancreatic secretion Cholecystokinin (CCK)-induced pancreatic secretion Liver cells Regulation of glucose metabolism Hepatic stellate cell Adrenal gland Adrenal cortex Adrenal medulla Insulin-secreting β-cells Islets of Langerhans Insulin release and biosynthesis Glucagon-secreting α-cells Airway epithelial cells White fat cells Brown fat cells Uncoupling proteins References for Module 7 8 Development Development encompasses the programme of events that begins with fertilization and culminates in complex multicellular organisms like ourselves. Synopsis Maturation Spermatozoan maturation Oocyte maturation Fertilization Sperm motility and chemotaxis Acrosome reaction Sperm-induced oocyte activation Completion of meiosis at fertilization Cell specification Ca2+ in embryonic development Dorsoventral specification Left–right asymmetry Planar cell polarity (PCP) Differentiation Proliferation–differentiation switch Signalsome expression Stem cells Embryonic stem cells Adult stem cells Stem cell niche Satellite cells Skin development Hair follicle cycle Skin regeneration and repair Epidermal stem cells Melanocyte stem cells Haematopoietic stem cell (HSC) HSC anchorage Intestinal stem cells Mesenchymal stem cell (MSC) Differentiation of bone cells Differentiation of intestinal cells Differentiation of skeletal muscle Differentiation of keratinocytes Differentiation of smooth muscle Differentiation of neurons Differentiation of white fat cells Differentiation of brown fat cells De-differentiation References for Module 8 9 Cell cycle and proliferation Cell proliferation is the process whereby cells reproduce themselves by growing and then dividing into two equal copies. Growth factors employ a range of growth factor signalling pathways to activate cells to enter the cell cycle. Synopsis Cell cycle Cell cycle events Prophase Prometaphase Metaphase Anaphase Telophase Cell cycle toolkit Cell cycle network Growth factor signalling/cell cycle interface Cell cycle signalling Cyclin D/cyclin-dependent kinase 4 (CDK4) activation Cyclin B/cyclin-dependent kinase 1 (CDK1) activation Cyclin D controls G1 progression Cyclin E controls G1 progression and DNA synthesis Cyclin A control of DNA synthesis Cyclin B/cyclin-dependent kinase 1 (CDK1) controls mitosis Cytokinesis Assembly and activation of a spindle midzone complex Assembly of the actomyosin contractile ring Activation of contraction Trafficking and insertion of membrane vesicles Cyclin-dependent kinase (CDK)-activating kinase (CAK) Polo-like kinases (Plks) Cyclin-dependent kinase (CDK) inhibitors Pocket proteins E2F family of transcription factors DNA damage and checkpoint signalling DNA damage Checkpoint signalling Cell proliferation. Information flow during proliferative signalling Growth factor signalling pathways K+ channels and cell proliferation Cell growth control Tuberous sclerosis complex 1 and 2 (TSC1/2) Target of rapamycin (TOR) Proliferation of specific cell types Lymphocyte activation T cell chemotaxis T cell cytoskeletal reorganization Immunological synapse T cell receptor (TCR) signalling Interleukin-2 (IL-2) signalling pathway References for Module 9 10 Neuronal signalling The central nervous system contains approximately one trillion (1012) neurons that are connected to each other to form neural circuits of bewildering complexity. Synopsis Neural circuits Cerebellum Hippocampus Neurogenesis Neuronal morphology Postsynaptic density (PSD) Neuronal endoplasmic reticulum Soma Synaptic endings Neuron-within-a-neuron Synaptic transmission Neuronal information transfer Neuronal Ca2+ entry and release channels Priming the inositol 1,4,5-trisphosphate receptors (InsP3Rs) and ryanodine receptors (RYRs) Neuronal coincident detection Input-specific signalling Presynaptic events Mossy fibre presynaptic Ca2+ release Cerebellar basket cell presynaptic Ca2+ release Hypothalamic neuronal presynaptic Ca2+ release Neocortical glutamatergic presynaptic Ca2+ release Miniature excitatory postsynaptic currents (mEPSCs) Dendritic transmitter release Postsynaptic events Postsynaptic changes in membrane potential Postsynaptic generation of Ca2+ signals Modulation of neuronal activity Neuronal excitability Facilitation Learning and memory Memory acquisition Neuronal coincident detectors Long-term depression (LTD) Long-term potentiation (LTP) Ca2+ and synaptic plasticity Memory consolidation Neural plasticity and drug addiction Medium spiny neurons Neuronal gene transcription Direct Ca2+-mediated gene transcription Indirect Ca2+-mediated gene transcription Neuronal protein synthesis Hypothalamic pituitary regulation Hypothalamus Posterior pituitary Anterior pituitary Sensory systems Olfaction Osmoreception Photoreception Rod and cone structure Phototransduction Cyclic GMP in phototransduction Hearing Nociception Chronic pain Hyperalgesia Touch Hypoxia-sensing mechanisms References for Module 10 11 Cell stress, inflammatory responses and cell death Cells have intrinsic signalling mechanisms that are capable of sensing various deleterious conditions, both normal and pathological, and respond by mounting a variety of stress responses. Synopsis Inflammatory responses Inflammatory cytokines Blood platelets Mast cells Mast cell release mechanisms Mast cell signalling mechanisms Macrophages Pathogen-associated molecular patterns (PAMPs) Modulation of inflammatory responses Neutrophils Neutrophil chemotaxis Senescence Replicative senescence Stress-induced senescence Autophagy Apoptosis Apoptotic signalling network Extrinsic pathway Intrinsic pathway Bcl-2 superfamily BH3-only family Bcl-2 superfamily control of Ca2+ signalling Caspase cascade Hormonal modulation of apoptosis References for Module 11 12 Signalling defects and disease A large number of diseases are caused by defects in signalling pathways. The nature of these defects and how they are induced varies enormously. Synopsis Pathogenic organisms and viruses Bacillary dysentery Cholera Listeriosis Peptic ulcers Tuberculosis Chlamydial diseases Signalsome remodelling and disease Phenotypic remodelling of the signalsome Alzheimer's disease Asthma Cirrhosis of the liver Cushing's syndrome Diabetes Diabetes insipidus (DI) Diabetic nephropathy Diarrhoea Drug addiction Ejaculatory dysfunction Endotoxic shock End-stage renal disease (ESRD) Epilepsy Erectile dysfunction Heart disease Humoral hypercalcaemia of malignancy (HHM) Irritable bowel syndrome Multiple sclerosis (MS) Nausea Primary hyperparathyroidism Secondary hyperparathyroidism Hypertension Manic-depressive illness (bipolar disease) Obesity Osteoporosis Pain Premature labour Rheumatoid arthritis Schizophrenia Sudden infant death syndrome (SIDS) Zollinger–Ellison syndrome Genotypic remodelling of the signalsome Achromatopsia Acute periodic paralysis Albinism Alport syndrome, mental retardation, midface hyperplasia and elliptocytosis (AMME) Amyotrophic lateral sclerosis (ALS) Anderman's disease Andersen-Tawil syndrome Angelman syndrome (AS) Arrhythmogenic ventricular cardiomyopathy type 2 (ARVD2) Ataxia telangiectasia (AT) syndrome Autosomal dominant hypocalcaemia (ADH) Bartter's disease Bernard–Soulier syndrome Brody disease Bruton's type X-linked agammaglobulinaemia Cancer Tumour cell microenvironment Catecholamine polymorphic ventricular tachycardia (CPVT) Central core disease (CCD) Charcot-Marie-Tooth disease 2A Charcot–Marie–Tooth disease 4B Concurrent generalized epilepsy with paroxysmal dyskinesia Congenital chloride diarrhoea Congenital hyperinsulinism of infancy Congenital insensitivity to pain Congenital lipoid adrenal hyperplasia Cowden's disease Craniofrontonasal syndrome (CFNS) Cystic fibrosis (CF) Darier's disease Dent's disease Dominant nonsyndromic deafness type 2 (DFNA2) Down's syndrome Early-onset obesity Episodic ataxia type 2 Erythermalgia Familial advanced sleep phase syndrome (FASPS) Familial Alzheimer's disease (FAD) Familial expansile osteolysis Familial hemiplegic migraine (FHM) Familial hypocalciuretic hypercalcaemia (FHH) Familial exudative vitreoretinopathy (FEVR) Familial focal segmental glomerulosclerosis (FSGS) Fanconi anaemia Fragile X syndrome (FXS) Frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) Gitelman's disease Glanzmann's thrombasthenia Glycogen storage disease Gordon's disease Gorlin's syndrome Hailey–Hailey disease Huntington's disease Huntington's disease-like 2 (HDL2) Hypogonadotropic hypogonadism Hypokalaemic periodic paralysis (HPP) Hypomagnesaemia hypercalciuria syndrome Hypomagnesaemia with secondary hypocalcaemia Kindler syndrome Lambert–Eaton myasthenic syndrome Leber congenital amaurosis (LCA) Liddle's disease Limb girdle muscular dystrophy type 2A Long QT syndrome Lowe's oculocerebrorenal (OCRL) syndrome Malignant hyperthermia (MH) Microcephaly Mucolipidosis Muscular dystrophy Myotonia congenita Neonatal severe hyperparathyroidism (NSHPT) Nephrogenic diabetes insipidus (NDI) Neurofibromatosis type 1 Neurofibromatosis type 2 Niemann–Pick disease Osteopetrosis Osteoporosis pseudoglioma (OPPG) Peutz–Jeghers syndrome Piebaldism Polycystic kidney disease Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) Prader-Willi syndrome (PWS) Progressive familial intrahepatic cholestasis type III (PFIC3) Respiratory distress syndrome (RDS) Retinitis pigmentosa Rett syndrome Scott syndrome Severe combined immune deficiency (SCID) Severe psychomotor retardation Sezary's syndrome Spinocerebellar ataxia type 6 (SCA6) Spinocerebellar ataxia type 12 (SCA12) Stargardt disease Tangier syndrome Timothy syndrome TNF-receptor-associated periodic febrile syndrome (TRAPs) Tuberous sclerosis Usher syndrome Van Buchem disease Waardenburg syndrome Wiskott–Aldrich syndrome X-linked adrenoleukodystrophy (X-ALD) X-linked mental retardation X-linked recessive myotubular myopathy X-linked severe combined immune deficiency (X-SCID) References for Module 12 Index |
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