Genetics Flashcards
What is germline mosaicism?
Parent cares AD gene mutation in their gonadal tissue and germline cells, but NOT in somatic cells–so they don’t show signs of disease.
Suspect when “normal” parent has more than 1 child affected with AD or X-linked condition.
What are some keys to look for on AR pedigree?
- will see disorders in 1 or more siblings but NOT in other generations
- males and females equally affected
- consanguinity increases risk of having offspring with disorder
What is genomic imprinting?
What are examples?
Genomic imprinting refers to difference in gene expression, depending on whether the disease allele is inherited from the mother or father.
Deletion of 2-4Mb portion of chromosome 15 inherited from father–> Prader-Willi syndrome = severe hypotonia, obesity, small hands and feet, MR
Deletion of 2-4Mb portion of chromosome 15 inherited from mother--> Angelman syndrome = normal until 6-12mo, then develop seizures, MR, hand flapping, ataxia, uncontrolled laughter (“happy puppet”)
Name the syndrome:
LGA, macrocephaly, prominent forehead, hypertelorism (increased distance b/t eyes), MR, large hands and feet
Sotos syndrome (AR)
Name the syndrome:
Coarse facies, macroglossia, ear lobe creases, posterior auricular pits, omphalocele, Wilms tumor, cryptorchidism, hemihypertrophy
Beckwith-Wiedemann syndrome (AD)
Name the syndrome:
Macrodactyly, soft tissue hypertrophy, hemihypertrophy, nevi, lipomas, hemangiomas, accelerated growth
Proteus syndrome
What are keys to look for in X-linked recessive pedigree?
- affected fathers transmit disease allele to all daughters (they are obligate carriers and usually unaffected) and no sons
- carrier females have 50% chance of transmitting disease to their sons
- there is no male-male transmission!
Common presentations for mitochondrial disorders include:
- metabolic encephalopathy
- lactic acidosis
- cardiac failure
- liver failure
What is this mitochondrial d/o that presents in infancy with anemia, neutropenia, pancreatic dysfunction, and myopathy?
Pearson syndrome
What is the mitochondrial d/o that presents with basal ganglia defects, hypotonia, and optic atrophy in infancy or early childhood?
Leigh syndrome
L
E ye problems
I nfancy/childhood
G anglia defects
H ypotonia
How is fragile X inherited?
What is the genetic abnormality?
X-linked inheritance; however 30% of carrier females have similar clinical phenotype to that of affected males
Caused by unstable CGG repeats on the FMR1 gene on the X chromosome
Normal = 6 to 50 repeats
Premutation = 55 to 200 repeats
Full mutation = > 200 repeats
What are common clinical findings of Fragile X?
- Large head
- MR
- Long face with large ears
- Large hands and feet
- Macroorchidism
- Hyperextensible joints
Think X-tra large!
Name 3 clinical disorders seen in premutation carriers of Fragile X (55 to 200 repeats).
- Mild cognitive and/or behavioral delays
- Premature ovarian failure
- FXTAS (fragile X associated tremor/ataxia syndrome) seen in older adult carriers who are mostly male and usually >50yo; clinical criteria includes intention tremor, gait ataxia, parkinsonism
What maternal serum results may indicate increased risk of Trisomy 21?
(high or low alpha, inhibin, hCG, estriol)
LOW alpha-fetoprotein
LOW unconjugated estriol
HIGH hCG
HIGH inHibin
What is the ratio or girls:boys in Edward’s syndrome (Trisomy 18)
4:1
