RARE GENETIC DISEASES - PART ONE

Medical Genetics, 6th Edition

CONTENTS

I. GENERAL PART
1. Rare genetic diseases - introduction. R. Stefanov, G. Iskrov, R. Vazharova, D.
Toncheva
1.1. Definition
1.2. Etiology
1.3. Epidemiology
1.4. RB prevention and screening programs
1.5. Genetic diagnosis of a number of RB
1.6. Patient organizations
1.7. Orphan drugs
1.8. EU policies on rare diseases
1.9. Rare diseases in Bulgaria

Genetics in Medicine: Thompson & Thompson – With Online Access, 7 edition
2. Genetic etiology of rare diseases. D. Toncheva, M. Pesheva, S. Lalchev
2.1. Point mutations.
2.2. Mutations affecting mRNA transcription, translation and maturation ………..
2.3. Mutations with an increased number of three nucleotide repeats
2.4. Mitochondrial mutations
2.5. Chromosome mutations
3. Diagnosis of rare genetic diseases. D. Toncheva, R. Vazharova, S. Hadzydekova, I. Dimova, M. Malinov
3.1. Standard genetic tests.
3.2. CNVs chips
3.3. SNPs-chips (genotyping chips)
3.4. Chips for methylation analysis
3.5. ChIP-on-chip chips
3.6. Sequencing with next generation sequencers (NGS – next generation sequencing)
4. Medical-genetic consultation. S. Lalchev, I. Dimova, M. Simeonova, B. Popov
4.1. Nature, purpose, tasks and organization of the MGK
4.2. Indications for genetic counseling
4.3. Principles and stages of genetic counseling
4.4. Making an accurate diagnosis
4.5. Training and risk assessment
4.6. Provide a conclusion and prevention advice
4.7. Tracking
4.8. Expertise of the genetic counselor
5. Genetic screening. I. Kremenski, M. Ivanova, I. Sinigerska, D. Dimitrov, S.
Andonova, R. Raynova, Ya. Petrova, I. Bradinova, A. Savov, I. Stoeva
5.1. Introduction
5.2. Mass biochemical screening of pregnant women
5.3. Mass neonatal screening
5.4. Selective extensive screening for the diagnosis of inborn errors of metabolism
5.5. Population genetic screening in the postgenomic era
6. Prenatal diagnosis.
6.1. Ultrasound examination during pregnancy. V. Dimitrova
6.2. Non-invasive prenatal test (NIPT). R. Vazharova, D. Toncheva
6.3. Invasive prenatal diagnosis. S. Hadzydekova, R. Vazharova, D. Toncheva
6.4. Assisted reproductive techniques (ART). Preimplantation diagnosis
(PGD) and preimplantation screening (PGS). S. Hadzydekova, G. Stamenov, D. Toncheva
7. Ethical, legal and psychological aspects in the diagnosis and prevention of
rare genetic diseases. B. Popov

II. Special part
8. Congenital anomalies E. Simeonov
8.1. Definition, terminology
8.2. Etiological classification of congenital anomalies
8.3. Dysmorphology in the era of genomic medicine /dysmorphology/
8.4. Molecular pathogenesis of congenital anomalies
8.5. Medico-social significance of congenital anomalies
8.6. Detection, treatment and prevention of congenital anomalies
9. Congenital diseases of the skeleton. E. Simeonov
9.1. Introduction
9.2. Epidemiology
9.3. Etiology and pathogenesis
9.4. Classification
9.5. Diagnosis of VSD
9.6. Clinical examples
9.7. Treatment of VSD
9.8. Prevention of VSD
9.9. Psycho-social problems of individuals with VSD
9.10. Genomic diagnosis of skeletal dysplasias. R. Vazharova, D. Toncheva
10. Hereditary connective tissue diseases. V. Ganev
10.1. MARFAN syndrome (MFS)
10.2. EHLERS-DANLOS syndrome
11. Hereditary diseases affecting tissue elastics: cutis laxa,
pseudoxanthoma elasticum and similar disorders. V. Ganev
11.1. Cutis laxa (OMIM 123700, 219100) and other loose skin syndromes
11.2. Pseudoxanthoma elasticum (OMIM 264500)
11.3. Buschke-Ollendorff syndrome (OMIM 166700).
11.4. Menkes syndrome
11.5. Williams syndrome (OMIM 194050) and supravalvular aortic stenosis
(SVAS, OMIM 185500).
11.6. Costello syndrome (OMIM 218040).
12. Chromosomal diseases. B. Popov, I. Dimova, R. Vazharova, V. Damyanova, D. Toncheva
12.1. Klinefelter syndrome
12.2. Fraccaro syndrome
12.3. "Superman" syndrome 47,XYY
12.4. Turner's syndrome 45, X
12.5. "Super" syndrome - trisomy X
12.6. Male pseudohermaphroditism - Morris syndrome (Morris) 46,ХУ
12.7. Female pseudohermaphroditism – 46,XX
12.8. True hermaphroditism - ovotestis
12.9. Down syndrome (Down) – Trisomy 21, 47, ХУ +21
12.10. Patau syndrome - Trisomy 13, 47, XY+13
12.11. Edwards syndrome (Edwards) – Trisomy 18 (47,XU,+18)
12.12. Wolf-Hirshhorn syndrome (Wolf - Hirshhorn) - 46,ХУ,4р-
12.13. Syndrome of the cat's meow (Sri du chat) - 46,ХУ, 5р-
11.14. Syndrome de Grouchy (Syndrome de Grouchy) – 46,XU,18p-
12.15. Rethore syndrome (Syndrome Rethore) 46,XU,9p+
13. Microdeletion/microduplication syndromes. S. Hadzydekova, R. Vazharova, D. Toncheva
13.1. Prader-Willi syndrome
13.2. Angelman syndrome (happy doll syndrome)
13.3. Williams-Beuren syndrome (Williams-Beuren syndrome)
13.4. Smith-Magenis syndrome
13.5. 22q11.2 - deletion syndrome (DiGeorge syndrome)
13.6. Miller-Dieker syndrome (Miller-Dieker syndrome)
13.7. Less common microdeletion syndromes
14. Registration of congenital anomalies – diagnostic and epidemiological aspects.
K. Kovacheva
15. Congenital metabolic diseases. M. Ivanova, I. Kremenski
16. Genomic diagnosis of VGM. R. Vazharova, D. Toncheva
17. Treatment of metabolic diseases. Radka Tincheva
17.1. Reduction of substrate accumulated in cells
17.2. Correction of substrate deficiency
17.3. Reduction of metabolic toxicity
17.4. Stimulation of residual enzyme activity
17.5. Enzyme replacement therapy in lysosomal diseases
17.6. Stem cell transplantation
17.7. Gene therapy
17.8. Treatment of mitochondrial diseases.
18. Lysosomal storage diseases. A laboratory approach to diagnosis. And.
Sinigerska, I. Kremenski
19. Genetics of autism spectrum disorders. D. Avdzhieva-Tzavella, S. Hadzydekova, R. Tincheva, D. Toncheva
19.1. Rett syndrome
19.2. Fragile X syndrome
19.3. Neurodermatoses
19.4. Prader-Willi / Angelman syndrome
19.5. Chromosomal diseases
19.6. Duchenne muscular dystrophy
19.7. Malformative syndromes
19.8. Metabolic diseases
19.9. Mitochondrial diseases
19.10. Mutations in genes encoding neurotransmitters and neuropeptides
19.11. Own research
19.12. Autism diagnosis with next-generation sequencing. R. Vazharova, D.
Toncheva
20. Mental retardation. L. Angelova
20.1. Causes of mental retardation
20.2. Light microscopic and submicroscopic chromosome analysis
20.3. Molecular genetic analysis by NGS diagnostic sequencing.
21. Genetic forms of epilepsy. I. Litvinenko
21.1. Genetic factors in the development of epilepsy
21.2. Febrile convulsions
21.3. Generalized epilepsy with febrile seizures plus (GEFS+)
21.4. Idiopathic generalized epilepsies (IGE)
21.5. Benign myoclonic epilepsy in early childhood - DMERDV
21.6. Autosomal dominant juvenile myoclonic epilepsy with GABRA1 mutation
21.7. Juvenile myoclonic epilepsy - UME
21.8. Childhood absence epilepsy - DAE
21.9. Juvenile absence epilepsy - UAE
21.10. Epilepsy with myoclonic absences
21.11. Myoclonic-astatic epilepsy - syndromic Dose (MAE)
21.12. Rolandic epilepsy (benign childhood focal epilepsy with
centrotemporal sharps, BECTS)
21.13. Autosomal dominant nocturnal fronto-lobular epilepsy ADNFLE .. 399
21.14. Temporal epilepsy (TE)
21.15. Familial focal epilepsy with variable focus - FFEVF
21.16. West syndrome
21.17. Genetic counseling of epileptic families
21.18. Genomic diagnosis of epilepsy. D. Toncheva, R. Vazharova
22. Hereditary ataxias. T. Chamova, V. Gergelcheva, I Tarnev
23. Hereditary spastic paraparesis. T. Chamova, I. Turnev
23.1. General characteristics of hereditary spastic paraparesis (Disease of
Strumpet)
23.2. Autosomal dominant hereditary spastic paraplegia due to mutations in the spastin gene (SPG4)
23.3. Autosomal dominant hereditary spastic paraplegia due to
mutations in the atlastin gene (SPG3A)
23.4. Autosomal recessive hereditary spastic paraplegia due to
mutations in the paraplegin gene (SPG7)
24. Hereditary myopathies and muscular dystrophies. T. Chamova, V. Gergelcheva, I. Tarnev
24.1. Progressive muscular dystrophies of Duchenne type and Becker type
24.2. Facioscapulohumeral dystrophy (FSHD)
24.3. Emery-Dreifuss muscular dystrophy
24.4. Girdle-limb progressive muscular dystrophies /PCMD/
24.5. Distal myopathies
24.6. Myotonic diseases
24.7. Metabolic myopathies
24.8. Congenital muscular dystrophies and congenital myopathies (VMD and VM)
25. Hereditary motor-sensory polyneuropathies V. Gergelcheva, I. Tarnev
26. Spinal muscular atrophies. T. Chamova, I. Turnev
27. Genomic diagnosis of neurological diseases. R. Vazharova, S. Ivanov, L. Balabanski, D. Toncheva