Unusual patterns of inheritance Flashcards
(22 cards)
Simply and usual patterns of inheritance?
What is mosaicism?
when a proportion, but not all, cells in an individual have a mutation, but the rest do not
Attenuated familial adenomatous polyposis?
De novo mutaion, causing a known dominant condition
Uniparental disomy?
Uniparental isodisomy = when a child inherits two copies of the same chromosome.
Example - Discovery of the chromosomal location of the Cystic Fibrosis gene:
Child described with both Silver-Russell Syndrome (SRS) and Cystic fibrosis (CF)
SRS known to be due to uniparental isodisomy of chromosome 7
Cystic fibrosis known to be recessive, but it was not known at the time as to which chromosome the CFTR gene was located on.
Co-occurrence of SRS and CF in same individual indicated that CFTR gene was on chr 7.
One of the parents must have been a carrier of a CFTR mutation, without of course showing any effects – but the child inheriting two copies of the mutation thus was affected with CF, a recessive condition.
Silver - Russell syndrome?
It is one of 200 types of dwarfism and one of five types of primordial dwarfism and is one of the few forms that is considered treatable in some cases.
Diagnosis:
Often small for gestational age (SGA) at birth (birth weight less than 2.8 kg)
Feeding problems: the baby is uninterested in feeding and takes only small amounts with difficulty
Hypoglycemia
Excessive sweating as a baby, especially at night, and a greyness or pallor of the skin. This may be a symptom of hypoglycemia
Triangular shaped face with a small jaw and a pointed chin that tends to lessen slightly with age. The mouth tends to curve down
A blue tinge to the whites of the eyes in younger children
Head circumference may be of normal size and disproportionate to a small body size
Wide and late-closing fontanelle
Clinodactyly
Body asymmetry: one side of the body grows more slowly than the other
Continued poor growth with no “catch up” into the normal centile lines on growth chart
Precocious puberty (occasionally)
Low muscle tone
Gastroesophageal reflux disease
A striking lack of subcutaneous fat
Late closing of the opening between the heart hemispheres
Constipation (sometimes severe)
Unipaental disomy?
when a child inherits both of one parent’s chromosomes
Genetic imprinting is a process which limits expression of some genes, depending on which parent they were inherited from. It is often involved in regulating growth. Normal size depends on inheriting one active and one inactive gene. The gene in question may only be active when inherited from, say, the father.
Inheriting two active genes may cause overgrowth, or the opposite if two inactive genes inherited. (This can also be caused by uniparental isodisomy.)
What is chimaera?
More than one individual in the same body
Examples of chimaerism?
Twins that share placental circulation
8% of non-ID twins are chimæric
Non-twins may have absorbed cells from a twin that died in utero
Mothers have lymphocytes from all their pregnancies.
Russia: “Citizen X”: Andrei Chikatilo (1994)
- blood and semen showed different blood groups
what is variable expression?
mutation is expressed as different conditions, e.g. diabetes, pancreatitis, pancreatic cancer with PRSS1 mutations
non-penetrance?
False negative
may be age related, e.g. % affected by age X
Whats is Sex Limitation?
mutation predisposes only one sex to disease
e.g. familial breast-ovarian cancer
What is phenocopies?
predisposed disease is common sporadically
e.g. familial bowel cancer
What is lymch syndrome?
pka Hereditary Non-Polyposis Colorectal Cancer (HNPCC)
Autosomal dominant
Reduced penetrance
Variable expression
Sex limited
Phenocopies
What is Waardenburd syndrome?
Variable expression
different colour eyes. pale retina in one.
Hereditary pancreatitis? Variable expression or non variable?
Variable
What is genetic impriting?
e.g. familial glomus tumours
Mutation is only expressed when inherited from father (or mother)
What is familial glomus tumours?
AD: Genetic Imprinting
Mutation in SDHD (11q23) only expressed when
inherited
from the father
Example of Xlinked dominant lethal inheritance?
Incontinentia pigmenti
Affects males abord in utero
New mutations arise in male germline
What is pseudodominance?
When a (common) recessive condition appears to transmit dominantly
What is matrilinear?
mother to child e.g. mitochondrial
Sperm do not transmit paternal mitochondria
Mitochondrial mutations can be heteroplasmic
- a form of mosaicism
- Russian Royal family identification
Proportion of mutant mitochondria passed on varies
- and hence clinical severity
Lebers hereditary optic atrophy?
Male predominance
