遺傳病之科學基礎及
診治
盧輝文醫生
衞生署醫學遺傳科高級醫生
孟德爾定律
1.
2.
分離律
獨立分配律
Gregor Johann Mendel
約翰·孟德爾
1822 - 1884
James Watson & Francis Crick
1953
Genome (基因組)
Human Genome Project
(人類基因組計劃)
1990
– 2003
Sped up gene discovery
estimated
~30,000 genes
Variations: ~0.1%
between any two
individuals
Types of genetic disorders
Chromosomal disorders (染色體異常)
Monogenic disorders (單基因遺傳病)
Multifactorial disorders (多種因素形成之疾
病)
Chromosomes (染色體)
Human beings have 46 chromosomes
22
pairs autosomes (常染色體)
1 pair sex chromosomes (性染色體)
Male - XY
Female - XX
染色體分析
染色體異常
Aneuploidy (數目異常)
E.g.
Down syndrome (唐氏綜合症), Turner
syndrome (特納氏綜合症)
Structural abnormalities (結構異常)
Deletion,
(易位)
duplication, inversion, translocation
螢光雜交技術 (FISH)
DNA 芯片 (Microarray)
Gene (基因)
1909 – Wilhelm Johanssen
Unit of genetic information
單基因遺傳病
Mendelian inheritance
Autosomal
dominant (常染色體顯性遺傳)
Autosomal recessive (常染色體隠性遺傳)
X-linked dominant (性連鎖顯性遺傳)
X-linked recessive (性連鎖隠性遺傳)
DNA (脫氧核糖核酸)
聚合酶鏈反應 (PCR)
電泳 (Electrophoresis)
DNA 序列 (sequencing)
Molecular testing in Genetic Laboratory, CGS
Diseases
Genes
Diseases
Genes
Fragile X-A syndrome
FMR1
Sex determination
SRY
Fragile X-E syndrome
FMR2
X-inactivation
Androgen receptor
Huntington disease
IT15
Polycystic kidney disease
Kennedy disease
Androgen receptor
PKD1(linkage)
PKD2 (linkage)
ARPKD (linkage)
Friedreich ataxia
X25
Leri-Weill syndrome
SHOX
Myotonic dystrophy
DMPK
Glutaric Aciduria type 1
GCDH
Pseudoachondroplasia
COMP
Haemophilia A
Factor VIII
Spinocerebellar ataxia
SCA1
SCA2
SCA3
SCA6
SCA7
SCA8
SCA12
Incontinentia pigmenti
NEMO
Alport syndrome
COL4A5 (linkage)
Neurofibromatosis type 1
NF1
Pyruvate dehydrogenase deficiency
PDHA1
Rett syndrome
MECP2
Gaucher disease
GCB
Noonan syndrome
PTPN11
Blepharophimosis-Ptosis-Epicanthus Inversus syndrome
FOXL2
Sotos syndrome
NSD1
Triple A syndrome
AAAS
Fabry’s disease
GLE
Dentatorubral-pallidoluysian atrophy
Duchenne Muscular Dystrophy
Charcot-Marrie-Tooth disease
Pelizaeus Merzbacher disease
Prader-Willi syndrome
Angelman syndrome
DRPLA
DMD
PMP22
MPZ
GJB1
PLP
Chromosome 15q11-q13
Chromosome 15q11-q13
Subtelomeric chromosomal deletion/duplication
Spinal muscular atrophy
SMN
α-Thalassaemia
HBA
β-Thalassaemia
HBB
Achondroplasia / Hypochondroplasia/ Thanatophoric dysplasia
FGFR3
Saethre-Chotzen syndrome
Twist
Trisomies 13, 18, 21
Craniosynostosis, syndromic
Marfan syndrome
Deafness, non-syndromic
GJB2, GJB6, mtDNA A1555G
NARP
PHOX2B
Conradi-Hunermann syndrome
EBP
Sshwartz-Jampel syndrome
LIFR
Spondylocostal dysplasia
DLL3
Metaphyseal dysplasia, McKusick type
RMRP
Pseudohypoparathyroidism
GNAS1
Diastrophic dysplasia
DTDST
Senior-Loken syndrome
IQCB1
Larsen syndrome
FLNB
FBN1
PAX3
MERRF
GLI3
Congenital Central Hypoventilation
FGFR2
Waardenburg syndrome type 1
MELAS
Greig syndrome
mtDNA A3243G
mtDNA A8344G
mtDNA T8993G
Management
Few chromosomal or single gene
disorders have curative treatment
Gene
therapy (基因治療)
Transplantation (移植)
Stem cell (幹細胞)
Prevention
Genetic
counselling (遺傳輔導)
Prenatal diagnosis (產前診斷)
衞生署醫學遺傳服務
Departmentof
ofHealth
Health
Department
衞生署
生署
衞
ClinicalGenetic
GeneticService
Service
Clinical
醫學遺傳服務
醫學遺傳服務
GeneticCounselling
CounsellingUnit
Unit
Genetic
遺傳輔導組
遺傳輔導組
GeneticLaboratory
Laboratory
Genetic
遺傳化驗所
遺傳化驗所
GeneticScreening
ScreeningUnit
Unit
Genetic
遺傳篩選組
遺傳篩選組
GeneticHealth
HealthPromotion
Promotion
Genetic
遺傳健康推廣
遺傳健康推廣
遺傳輔導組
GeneticCounselling
CounsellingTeam
Team
Genetic
Consultant
Consultant
顧問醫生
顧問醫生
SM&HO
SM&HO
高級醫生
高級醫生
SM&HO
SM&HO
高級醫生
高級醫生
M&HO
M&HO
醫生
醫生
M&HO
M&HO
醫生
醫生
NO
NO
護士
護士
遺傳輔導組
The only service in HK and in China that
provides comprehensive genetic services on
a territory-wide basis, playing a primary role
in genetic diagnosis, counselling and
prevention.
By referral (轉介) from other medical
professionals
Clinic Locations
1/F Cheung Sha Wan Jockey Club
Clinic
Satellite clinics
Queen
Elizabeth Hospital, KLN
4/F Ambulatory Care Centre
L-blk
Clinic Set-up
20-22 clinic sessions / m
~1,200
new cases / yr
~2,300 follow-up cases / yr
1981-2006
23,505
families attended
Our Clients
30%
70%
兒童
成人
Types of Disorders (以病原分類 )
Chart 1
70, 0%
3358, 14%
Teratogenic
Single gene disorders
4317, 18%
11317, 49%
Chromosomal disorders
Multifactorial
Unknown / undefined
4443, 19%
Types of Disorders (以系統分類 )
Chart 2
4500
4000
3500
3000
2500
2000
1500
1000
500
0
Ch Me Oth En Dia Fet Gr No Ne Ha Sk Ne Cr Op Co De Ca Me De Re Ga Te Im Re
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MC
A
遺傳輔導的定義
Peter Harper
“Genetic counselling is the process by which patients or
relatives at risk of a disorder that may be hereditary are
advised of the consequences of the disorder, the probability
of developing or transmitting it and of the ways in which this
may be prevented, avoided or ameliorated.”
Preventive medicine (預防性醫學)
遺傳輔導
Provide ample information for patients or family
members to make fully informed decisions
Diagnosis,
natural course
Hereditary or not
Mode
Risk
of inheritance (遺傳模式)
of recurrence (復現風險)
Prenatal diagnosis or PGD (產前/植入前遺傳診斷)
Contraception, sterilization, alternative reproductive
options
Assess other family members at risk
Fetal ultrasound
Prevalence of Genetic Disorders
Chromosomal disorders (染色體異常 )
Monogenic disorders (單基因遺傳病 )
Multifactorial disorders (多種因素形成
之疾病 )
3.8 / 1,000
20 / 1,000
650 / 1,000
多種因素形成之疾病
Genetic
mutations/variation
+ Environmental factors
Disease
Genomics
The study of all the genes in a person, as
well as interactions of those genes with
each other and with that person’s
environment.
Plays a part in nine of the ten leading
causes of death in the US.
10 leading causes of death (HK, 2004)
Genetic susceptibility (易感性)
All human beings are 99.9% identical in
genetic makeup, but differences in the
remaining 0.1% may hold important clues
about the causes of disease.
Public Health Genetics
Genetic testing
Identify susceptible population
Intervention
Prevention
Healthier population
Acknowledgment
Dr. S. Lam, Consultant Clinical Geneticist
Genetic Counselling Team
Genetic Laboratory