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E-raamat: Atlas of Inherited Retinal Diseases

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This Atlas of Inherited Retinal Disorders provides a thorough overview of various inherited retinal dystrophies with emphasis on phenotype characteristics and how they relate to the most frequently encountered genes. It also meets the previously unmet needs of PhD students who will benefit from seeing the phenotypes of genes they work on and study. Further, because genetic-testing costs are quite high and spiraling higher, this Atlas will help geneticists familiarize themselves with the candidate gene approach to test patients’ genomes, enabling more cost-efficient testing. This invaluable atlas is organized into eight sections starting with an introduction to the basic knowledge on retinal imaging, followed by diseases listed according to inheritance pattern and disorders with extraocular manifestations grouped by defining features. This structure will be intuitive to clinicians and students studying inherited retinal disorders.


Section I Basic Knowledge
Retinal Histology and Anatomical Landmarks
3(4)
Retinal Layers
4(1)
Bruch's Membrane
4(1)
Choroid
4(1)
Anatomical Landmarks of The Macula
4(1)
Did You Know?
5(1)
Suggested Reading
5(2)
Fluorescein Angiography
7(4)
Principle and Technique
8(1)
Dye-Transit Phases
8(2)
Blood-Retinal Barrier
10(1)
Suggested Reading
10(1)
Optical Coherence Tomography
11(4)
Historical Perspective
12(1)
Principle
12(1)
Normal OCT Scans
12(1)
Suggested Reading
13(2)
Fundus Autofluorescence
15(6)
Suggested Reading
16(1)
Electroretinography
17(1)
Full-Field ERG
18(1)
Pattern ERG
18(1)
Multifocal ERG
19(1)
Suggested Reading
20(1)
Electrooculography
21(10)
Suggested Reading
22(1)
Glossary of Relevant Genetic and Molecular/Cell Biology
23(1)
Genetics
24(1)
Genetic Disorders
25(1)
Molecular Biology
26(1)
Inheritance
27(1)
Diagnosis and Treatment
27(4)
Section II X-linked Forms
X-linked Retinitis Pigmentosa
31(6)
General Features
32(1)
Female Carriers
32(1)
Molecular Genetics
33(1)
RPGR Gene
33(1)
RP2 Gene
33(1)
Gene Therapy Trials
33(1)
Did You Know?
33(2)
Suggested Reading
35(2)
X-linked Choroideremia
37(6)
General Features
38(1)
Imaging and Tests
39(1)
Female Carriers
39(1)
Molecular Genetics
40(1)
Gene Therapy Trials
40(2)
Suggested Reading
42(1)
X-linked Juvenile Retinoschisis
43(6)
General Features
44(2)
Imaging and Tests
46(1)
Molecular Genetics
46(1)
Treatments
46(2)
Oral Acetazolamide
46(2)
Vitreoretinal Surgery
48(1)
Gene Therapy
48(1)
Suggested Reading
48(1)
X-linked Ocular Albinism
49(4)
General Features
50(1)
Female Carriers
50(1)
Oculocutaneous Albinism
50(1)
Molecular Genetics
50(2)
Ocular Albinism
50(1)
Oculocutaneous Albinism
51(1)
Suggested Reading
52(1)
Progressive Cone Dystrophy and Cone-Rod Dystrophy (XL, AD, and AR)
53(8)
General Features
54(3)
Molecular Genetics
57(1)
Specific Genotype and Phenotype Correlation
58(2)
ABCA4
58(1)
ADAM9 (CORD9)
58(1)
RPGRIPI (CORDI3, Leber Congenital Amaurosis [ LCA6])
58(1)
KCNV2 (Potassium Voltage-Gated Channel Modifier Subfamily V Member 2)
58(1)
SEMA4A (Semaphoring 4A) (CORD 10 or RP35)
58(1)
GUCY2D (CORD6 or LCAI or RCD2)
58(1)
GUCAIA (Guanylate Cyclase Activator IA) (COD4 or CORD 14)
59(1)
PRPH2 (Peripherin 2 or RDS)
59(1)
CRX (CORD2 or LCA7 or CRD)
59(1)
RIMSI (Regulating Synaptic Membrane Exocytosis I, CORD7)
59(1)
PITPNM3 (CORD5)
59(1)
RPGR (CODI or CORCXI or RP3 or RP1I5 or XLRP3)
59(1)
Suggested Reading
60(1)
Congenital Stationary Night Blindness
61(4)
Congenital Stationary Night Blindness with Normal Fundi
62(1)
Types
62(1)
Molecular Genetics
62(1)
Congenital Stationary Night Blindness with Abnormal Fundi
63(1)
Fundus Albipunctatus
63(1)
Oguchi Disease
64(1)
Suggested Reading
64(1)
Blue Cone Monochromatism
65(4)
General Features
66(1)
Imaging and Tests
66(1)
Molecular Genetics
66(1)
Suggested Reading
66(3)
Section III Autosomal Dominant Forms
Autosomal Dominant Retinitis Pigmentosa
69(10)
General Features
70(1)
Molecular Genetics
70(7)
RHO Gene (RP4, Opsin-2)
70(1)
PRPF3 Gene (RP 18, SNRNP90)
70(1)
RP/Gene (ORPI)
70(7)
Suggested Reading
77(2)
Best Vitelliform Macular Dystrophy
79(12)
General Features
80(1)
Imaging and Tests
80(7)
Subtypes
87(1)
Adult-Onset Foveomacular Vitelliform Dystrophy (AFMD)
87(1)
Autosomal Recessive Bestrophinopathy (ARB)
87(1)
Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC)
87(1)
Molecular Genetics
87(3)
bESTI Gene (VMD2 Gene or RP50 or HMD)
87(3)
PRPH2 Gene (Peripherin 2 or RDS or CACD2 or Tetraspanin-22)
90(1)
Suggested Reading
90(1)
Pattern Dystrophy
91(6)
General Features
92(4)
Butterfly-Type Pattern Dystrophy
92(4)
Adult-Onset Foveomacular Vitelliform Dystrophy
96(1)
Sjogren's Reticular-Type Pattern Dystrophy
96(1)
Fundus Pulverulentus
96(1)
Molecular Genetics
96(1)
PRPH2 Gene (Peripherin/RDS or rd2 or Peripherin-2 or RDS)
96(1)
Suggested Reading
96(1)
Doyne Honeycomb Retinal Dystrophy (Malattia Leventinese, Autosomal Dominant Drusen)
97(6)
General Features
98(4)
Molecular Genetics
102(1)
EFEMPI Gene (DHRD or DRAD or FBLN3 or FIBL-3)
102(1)
Suggested Reading
102(1)
Occult Macular Dystrophy
103(2)
General Features
104(1)
Molecular Genetics
104(1)
Suggested Reading
104(1)
Sorsby Pseudoinflammatory Fundus Dystrophy
105(4)
General Features
106(1)
Molecular Genetics
106(2)
TIMP3 Gene (K222 or SFD)
106(2)
Suggested Reading
108(1)
North Carolina Macular Dystrophy
109(2)
General Features
110(1)
Molecular Genetics
110(1)
Suggested Reading
110(1)
Pigmented Paravenous Chorioretinal Atrophy (PPCRA)
111(4)
General Features
112(1)
Molecular Genetics
112(1)
Suggested Reading
113(2)
Late-Onset Retinal Degeneration
115(4)
General Features
116(1)
Molecular Genetics
116(1)
CIQTNF5 Mutation (CTRP5)
116(1)
Suggested Reading
116(3)
Section IV Autosomal Recessive Form
Rod Monochromatism (Achromatopsia)
119(6)
General Features
120(1)
Stages
120(1)
Molecular Genetics
120(3)
Gene Therapy Trials
123(1)
Suggested Reading
123(2)
Retinitis Pigmentosa (Non-syndromic)
125(14)
General Features
126(1)
Genes and Mutations
126(4)
PDE6 (Phosphodiesterase)
126(1)
RP25 or EYS (Eyes Shut Homolog)
126(1)
TULPI (Tubby-Like Protein I) Gene or RP14 or TUBLI or LCA/5
126(1)
CERKL (Ceramide Kinase-Like) Gene or RP26
126(1)
RPE65 Gene
127(1)
Other Genes Associated with AR-RP
127(3)
Suggested Reading
130(1)
Leber Congenital Amaurosis
131(8)
General Features
132(1)
Molecular Genetics
132(1)
Specific Genotype and Phenotype Correlations
132(1)
LCA1
132(1)
LCA2
132(1)
LCA3
132(1)
LCA4
132(1)
LCA5
133(1)
LCA6
133(1)
LCA7
133(1)
LCA8
133(1)
LCA9
133(1)
LCA10
133(1)
LCA11
133(1)
LCA12
133(1)
LCA14
134(1)
LCA15
134(1)
LCA16
134(1)
RP38
135(1)
LCA57
135(2)
SLSN5
137(1)
Suggested Reading
137(2)
Stargardt Disease
139(14)
General Features
140(1)
Clinical Stages and Groupings
140(5)
Stages, Based on Fundus Appearance
140(5)
Groupings, Based on Electroretinography (ERG)
145(1)
Types, Based on FAF
145(1)
Classes, Based on Optical Coherence Tomography (OCT)
145(1)
Molecular Genetics
145(6)
A&CA4 Gene (RIM Protein or ABCR)
145(4)
Other Mutations
149(1)
Genotype-Phenotype Correlation
149(2)
Suggested Reading
151(2)
Enhanced S-Cone Syndrome (Goldmann-Favre Syndrome)
153(4)
General Features
154(1)
Molecular Genetics
154(2)
Suggested Reading
156(1)
Best Vitelliform Macular Dystrophy
157(4)
General Features
158(1)
Suggested Reading
158(3)
Section V Systemic Disorders
Mitochondrial Disorder: Kearns-Sayre Syndrome
161(2)
General Features
162(1)
Molecular Genetics
162(1)
Suggested Reading
162(1)
Mitochondrial Disorder: Maternally Inherited Diabetes and Deafness
163(4)
General Features
164(1)
Molecular Genetics
165(1)
Suggested Reading
165(2)
Ciliopathy: Usher Syndrome
167(4)
General Features
168(1)
Molecular Genetics
169(1)
USH1
169(1)
USH2
170(1)
USH3
170(1)
Suggested Reading
170(1)
Gliopathy: Bardet-Biedl Syndrome
171(4)
General Features
172(1)
Molecular Genetics
172(2)
Suggested Reading
174(1)
Ciliopathy: Senior-Løken Syndrome
175(4)
General Features
176(1)
Molecular Genetics
176(2)
Suggested Reading
178(1)
Ciliopathy: Alstrom Syndrome
179(2)
General Features
180(1)
Molecular Genetics
180(1)
Suggested Reading
180(1)
Ciliopathy: Sjogren-Larsson Syndrome
181(2)
General Features
182(1)
Molecular Genetics
182(1)
Suggested Reading
182(1)
Inborn Errors of Metabolism: Gyrate Atrophy
183(4)
General Features
184(1)
Molecular Genetics
184(1)
Suggested Reading
184(3)
Inborn Errors of Metabolism: Pseudoxanthoma Elasticum
187(4)
General Features
188(1)
Molecular Genetics
189(1)
Suggested Reading
189(2)
Inborn Errors of Metabolism: Refsum Disease
191(2)
General Features
192(1)
Molecular Genetics
192(1)
Suggested Reading
192(1)
Inborn Errors of Metabolism: Bietti Crystalline Dystrophy
193(4)
General Features
194(1)
Molecular Genetics
194(1)
Suggested Reading
195(2)
Extracellular Matrix: Alport Syndrome
197(4)
General Features
198(1)
Molecular Genetics
198(1)
Suggested Reading
198(3)
Section VI Phakomatoses
Von Hippel-Lindau Disease
201(4)
General Features of Phakomatoses
202(1)
General Features of Von Hippel-Lindau Disease
202(1)
Molecular Genetics of Von Hippel-Lindau Disease
203(1)
Suggested Reading
203(2)
Tuberous Sclerosis
205(4)
General Features
206(1)
Molecular Genetics
206(1)
Suggested Reading
207(2)
Neurofibromatosis
209(6)
General Features
210(1)
Neurofibromatosis Type I
210(1)
Neurofibromatosis Type 2
210(1)
Molecular Genetics
210(1)
Suggested Reading
211(4)
Section VII Phenocopies
Rubella Retinopathy
215(4)
General Features: Phenocopies
216(1)
General Features: Rubella Retinopathy
216(1)
Suggested Reading
217(2)
Syphilis
219(4)
General Features
220(1)
Suggested Reading
220(3)
Autoimmune Retinopathy
223(4)
General Features: Autoimmune Retinopathies
224(1)
Paraneoplastic Retinopathy
224(1)
Non-paraneoplastic Autoimmune Retinopathy
224(2)
Suggested Reading
226(1)
Drug-Induced Retinal Toxicity
227(6)
General Features
228(1)
Damage to RPE and Photoreceptor Complex
228(1)
Damage to the Vascular Bed or Microvasculopathy/Occlusion
229(2)
Damage to Ganglion Cell Layer or Optic Nerve
231(1)
Drugs Causing Cystoid Macular Edema
232(1)
Drugs Causing Crystalline Retinopathy
232(1)
Drugs Causing Uveitis
232(1)
Suggested Reading
232(1)
Acute Zonal Occult Outer Retinopathy (AZOOR) and Related Diseases
233(6)
General Features
234(1)
AZOOR Complex
235(2)
Suggested Reading
237(2)
Diffuse Unilateral Subacute Neuroretinitis (DUSN)
239(6)
General Features
240(1)
Suggested Reading
241(4)
Section VIII Managing IRDs in Clinics
A Practical Approach to Retinal Dystrophies
245(16)
Examination and Testing
246(1)
Stationary Retinal Dystrophies
246(3)
Stationary Rod Dystrophies
246(1)
Stationary Cone Dysfunction Syndromes
247(2)
Progressive Retinal Dysfunction
249(2)
Central Dystrophies
251(4)
Stargardt Disease
251(1)
Other Central Dystrophies
252(3)
Treatments
255(2)
Dietary Treatment and Vitamins
255(1)
Treatment of Complications
255(1)
Gene Therapy
256(1)
Other Emerging Therapies
257(1)
Summary
257(1)
References
257(4)
Genetic Testing for Inherited Retinal Dystrophy: Basic Understanding
261(8)
What Is Genetic Testing?
262(1)
Which Retinal Diseases Would Benefit from Genetic Testing?
262(1)
What Is the Role of the Ophthalmologist in Genetic Testing?
262(1)
What Are the Benefits of a Genetic Test?
262(1)
What Are the Risks of Genetic Testing?
263(1)
Does Everyone with the Same Diagnosis Have the Same Genetic Mutation?
263(1)
What Information Is Given by Genetic Testing?
263(1)
What Are the Types of Genetic Testing?
263(1)
What Are the Structure and Function of the Genome?
264(1)
Structure
264(1)
Function
264(1)
What Is Genomic or Genetic Variation?
264(1)
Does Every Variation Result in a Disease?
265(1)
How Are Genomic Variants Classified in a Genetic Report?
265(1)
Are Further Investigations Needed After the Genetic Testing?
265(1)
Understanding the Genetic Testing Report
265(3)
What Is a Genetic Code?
265(1)
What Is Polymorphism?
265(1)
What Is a Mutation?
265(1)
How Are Reference Sequence Variants Reported or Described?
265(3)
Reference
268(1)
Suggested Reading
268(1)
Index 269
Stephen H. Tsang MD, PhD has been culturing embryonic stem (ES) cells since 1992 and in 1995 created the first mouse model for a recessive form of retinitis pigmentosa (RP) by applying homologous recombination to ES cell technology. Since 1996, the Dr. Tsang has been quantifying retinal function and structure in gene-targeted mutant mice. As the director an international referral center for inherited retinal degenerations, Dr. Tsang cares for a specific subgroup of patients that are most appropriately aligned with precision medicine. At times, patients suffer from a disorder that is related to an existing transgenic mouse model generated in the laboratory, and other times patients inspire new models. . Dr. Tsang's contributions to genetics has being recognized by the 2005 Bernard Becker-Association of University Professor in Ophthalmology-Research to Prevent Blindness Award, Carl Camras Award, and the 2013 Bradley Straatsma Lectureship.  Dr. Tsang received 2008 resident teaching award. He is also a standing member of the DPVS study section at NIH, American Society for Clinical Investigation, American Ophthalmological Society and Macular Society. Tarun Sharma For over three decades, Tarun Sharma was associated with a tertiary eye care institute SANKARA NETHRALAYA Chennai, India. He was the director of vitreoretinal services and professor of ophthalmology for over a decade. For his distinguished contribution to the field of ophthalmology, he was awarded thrice by the American Academy of Ophthalmology: Achievement Award (2007), International Ophthalmologist Education Award (2009), and the International Scholar Award (2011). In 2017, he joined the Edward S. Harkness Institute, the Columbia University Medical Center, NY, and currently working as a gene therapist at Jonas Children's Vision Care.