Clinical genetics in medical practice 1 Flashcards

1
Q

Define Karyotype

A

The number and visual appearance of the chromosomes in the cell nuclei of an organism or species

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2
Q

Define mutation

A

A pathogenic(heritable) alteration in the gene affecting the structure or the function of a protein.

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3
Q

What are the characteristics of autosomal dominant conditions

A
  • Caused by a mutation in a single autosomal gene
  • Affected individuals are heterozygous for the mutation
  • They have a normal(wild) type and a mutant copy of the gene
  • Transmitted from generation to generation( i.e vertical inheritance)
  • Males and females are usually affected equally
  • Affected parent of either sex can transmit the disorder to both sons and daughters
  • 1 in 2 (50%) risk of an affected parent transmitting the condition to his/her children
  • Key feature= male-to-male transmission
  • Variable (reduced) penetrance
  • Variable expression
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4
Q

What is reduced penetrance?

A
  • Penetrance is a statistic and is usually expressed as a %
  • The proportion of carriers who manifest phenotypic signs of the condition
  • Not all individuals who inherit a dominant disease mutation necessarily show signs of the condition
  • There may be age-specific penetrance
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5
Q

What are some of the characteristics of cherubism and its inheritance?

A
  • A genetic abnormality
  • Occurs as an autosomal dominant disorder and with 100% pentrance in males and 50 to 75% penetrance in females with 2:1 male predominance
  • Marked fullness of the jaws
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6
Q

What is variable expression/ expressivity?

A
  • Extent of clinical manifestation

- Variable within and between families

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7
Q

What are the 4 defects in Tetralogy of Fallot?

A

-Thick right ventricle (hypertrophy)
-Ventricular septal defect (VSD)
-Pulmonary stenosis(narrow pulmonary valve)
-Large overriding aorta.
This leads to reduced pulmonary blood flow due to a narrow outlet

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8
Q

What is germline mosaicism?

A

A parent carries a small proportion of gametes(germline cells) that harbour the same mutation

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9
Q

What are the characteristics of autosomal recessive conditions?

A
  • Males and females can be equally affected
  • Generally only members of a single sibship, or cousins affected(unless multiple consanguinity in the family)
  • The probability that a future sibling of an affected individual will also be affected is 1 in 4
  • The probability that a future sibling will be a carrier is 1 in 2
  • The probability that an existing unaffected sibling is a carrier is 2 in 3 (the denominator changes as we have excluded the affected individual from our calculation)
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10
Q

What is compound heterozygosity?

A

-Someone who has different allelic mutations at the same locus

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11
Q

What are the characteristics of X-linked recessive disorders?

A
  • Only males related via the female line are usually affected
  • Women are usually asymptomatic
  • 1 in 2 chance that each son born to a carrier female will be affected
  • 1 in 2 chance that each daughter will be a carrier
  • All the daughters of an affected male will be carriers
  • Sons of an affected male are not affected (no male-male transmission)
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12
Q

How can females be affected with X-linked recessive disorders?

A
  • Non-random inactivation leading to chance expression in certain tissues e.g expression of mutant allele in: heart in Duchenne Muscular dystrophy carriers; Kidney in X-linked Alport’s disease; brain in fragile X syndrome(learning disability)
  • Turner’s syndrome 45,X
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13
Q

What is X inactivation?

A
  • Only one X used per cell in 46 XX or 47XXY
  • Idea of dosage compensation
  • One X in each cell is switched off before blastocyst implants in females
  • All women are mosaics, expressing either their maternal or paternal X but not both in any one of their cells
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14
Q

Explain the idea of random X inactivation

A
  • One X chromosome per cell is inactivated by methylation
  • All of its daughter cells have the same X chromosome inactivated (i.e they are a clone of cells with the same pattern of inheritance)
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15
Q

What are the characteristics of X-linked dominant disorders?

A
  • Males and females affected (males>females)
  • Affected females can show a mosaic pattern of involvement in tissues such as skin
  • The condition may be lethal in males
  • 50% offspring risk to males and females of affected mothers
  • All daughters of affected males inherit the condition
  • None of the sons of affected males inherit the condition.
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16
Q

What are lines of Blaschko

A
  • represent territories of clonal cell populations: some using normal X chromosome, some using mutated X chromosome
  • Can be manifest in X-linked dominant disorders e.g Incontinentia Pigmenti and Goltz focal dermal Hypoplasia.