Inheritance Flashcards
Cystic Fibrosis - what is the inheritance?
Autosomal recessive
Cystic Fibrosis- what are the key characteristics?
Autosomal recessive, mutation in the CTFR (cystic fibrosis transmembrane conductance regulator) gene on chromsome 7, the most common mutation is deletion of F508 (delta F508 mutation in 70% of cases) - excess mucus production and chloride in sweat - recurrent chest infections, poor gas exchange, pancreatitis, cirrhosis, intestinal obstruction, malabsorption of fat soluble ADEK vits, osteoporosis, diabetes, Infertility
Why does CF lead to infertility?
Absent vas deferens (men), thickened cervical mucus (women)
Fragile X syndrome - what is the inheritance?
X-linked dominant (but features less prominent in females, some texts refer to the condition as recessive)
Fragile X syndrome - what are the characteristics?
FMR1 mutation, X-linked dominant inheritance but phenotype suppressed in females so some texts refer to as recessive- long face, protruding ears, enlarged testes(macroorchidism), low muscle tone, flat feet, learning difficulties, may have autism adhd, seizures
Duchenne’s Muscular Dystrophy - what is the inheritance?
X-linked recessive
Duchenne’s Muscular Dystrophy - what are the characteristics?
X-linked recessive inheritance, progressive neuromuscular disorder, weakness and wasting affecting the hip and shoulder girdle first. Mutation of the dystrophin Xp21 gene
What are the features of X-linked recessive inheritance?
Only males are affected, females can be carriers, fathers can not pass the recessive gene onto sons, only mothers can transfer the gene. Knight’s move pattern of inheritance = any male grandchild of an affected male
Turner syndrome- what is the inheritance?
Chromosomal abnormality (sex chromosome aneuploidy) - 45 X0
Turner Syndrome - what are the characteristics
Sex chromosome aneuploids 45X0 (monosomy X), typically caused by loss of a Barr body - raised nuchal translucency, neck webbing, cystic hygroma, short stature, wide carrying arm angle, shield shaped chest, normal intelligence, infertility and prevention of developing female sex characteristics due to gonadal dysgenesis (loss of germ cells on developing embryo), horshoe kidney, cardiac abnormalities, 1 in 2500 live births but 90% will miscarry before term
Christmas disease - what is the inheritance?
X-linked recessive inheritance
Christmas disease - what are the characteristics?
X-linked recessive inheritance, factor XI deficiency haemophilia B (second most common haemophilia)
Prader-Willi syndrome - what is the inheritance?
Chromosomal microdeletion
Prader-Willi syndrome - what are the characteristics?
Chromosomal microdelition, chromosome 15, obesity, type 2 diabetes, may have learning difficulties, lack of sexual development, due to gene deletion (paternally deleted genes and maternal imprinting)
What is chromosomal microdeletion?
A genetic abnormality caused by deletion of a small sub-set of genes located near to each other on a chromosome accounting for the deletion of less than 5 million base pairs
Angelman syndrome - what is the inheritance?
In many cases it is caused by chromosomal microdeletion (maternal gene deletion rather than paternal gene deletion seen in Prader-Willi syndrome)
Cri-du-chat syndrome - what is the inheritance?
Chromosomal microdeletion on short arm of chromosome 5
Angelman syndrome - what are the characteristics?
Predominately caused by a chromosomal microdeletion on the maternal gene with paternal imprinting - results in a neurodevelopmental disorder, severe developmental delay, happy demeanor, elf-like features
Cri-du-chat syndrome
Chromosomal microdeletion on chromosome 5 (short arm), developmental delay, small head and jaw, characteristic cry
When is nuchal translucency measured?
Between 11-14 weeks
What conditions are associated with increased nuchal translucency?
Down’s syndrome, Patau syndrome, Edward’s syndrome, Turner syndrome, Noonan syndrome, major cardiac abndomalities
Noonan syndrome - what is the inheritance?
Autosomal dominant
Noonan syndrome - what are the characteristics?
Autosomal dominant inheritance (most commonly), several different genes with KRAS gene mutation being the most common, clinical features include short stature, congenital heart defects, wide brow, neck webbing, low set ears
What is the most common cause of trisomy?
Non-disjunction during meiosis 1
What is the most common trisomy to result in miscarriage?
Trisomy 16
What is the most common trisomy compatible with life?
Trisomy 21
Kleinfelter’s syndrome - mode of inheritance
Sex chromsome aneuplody 47XXY
Kleinfelter’s syndrome- what are the characteristics?
Tall, small testes (hypogonadotrophic hypogonadism), infertility
Red-green colour blindness - mode of inheritance
X-linked recessive
Infantile polycystic kidney disease - what is the mode of inheritance and what are the characteristics
Autosomal recessive inheritance, enlarged polycystic kidneys, reduced amniotic fluid, underdeveloped lungs, underdeveloped liver, internal bleeding, reduced life expectancy (most will dies in infancy)
Osteogenesis imperfecta - mode of inheritance
Autosomal dominant
Osteogenesis imperfecta - what are the characteristics?
autosomal dominant inheritance, blue sclera, brittle bones that break easily, multiple different types but most common mutation on COL1A1
Beta Thalassaemia - mode of inheritance
Autosomal recessive
Which gene is affected in fragile x syndrome?
FMR1 gene on the X chromosome which codes for FMRP protein, important for building synapses in the brain. In normal fmr1 genes there is a cgg repeat 5 to 40 times but when mutated in fragile X it is repeated over 200 times making the gene unable to produce the FMRP protein
Congenital adrenal hyperplasia - what is the inheritance?
autosomal recessive
Congenital adrenal hyperplasia - what is the most common gene/protein affected?
CYP21A gene - 21-hydroxylase (resulting in androgen excess and mineralcorticoid deficiency)
Phenylketonuria - inheritance
autosomal recessive
Test for PKU
guthrie (heel prick test) done after 12 hours of birth, usually within 5 days
Consequences of PKU
error in amino acid metabolism - severe deficiency in phenylalanine hydroxalase and therefore cannot metabolism phenylalanie resulting in a build of phenylpyruvic acid and phenylethylamine, which become neurotoxic in high concentrations. Untreated, this can result in learning difficulties and seizures
