Achondroplasia Inheritance Patterns

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Questions and Answers

What percentage of people with achondroplasia have average-size parents?

80% (correct)

50%

20%

90%

What is the pattern of inheritance of achondroplasia?

Autosomal dominant (correct)

X-linked dominant

Autosomal recessive

Mitochondrial

What is the genetic basis of cystic fibrosis?

Mutations in the Hemochromatosis gene

Mutations in the CFTR gene (correct)

Mutations in the FGFR3 gene

Mutations in the Tay-Sachs gene

What is the pattern of inheritance of cystic fibrosis?

Autosomal recessive Signup and view all the answers

What is a characteristic of autosomal recessive disorders?

They clinically manifest only when a person has two copies of the mutant allele Signup and view all the answers

What is a characteristic of autosomal dominant disorders?

One mutated copy of the gene in each cell is sufficient for a person to be affected Signup and view all the answers

What is a common sign and symptom of cystic fibrosis?

Chronic digestive system problems Signup and view all the answers

Which of the following is an example of an autosomal recessive disease?

Cystic fibrosis Signup and view all the answers

Which of the following is an example of an autosomal dominant disorder?

Huntington disease Signup and view all the answers

What is the function of the CFTR gene in cystic fibrosis?

It provides instructions for making a channel that transports chloride ions into and out of cells Signup and view all the answers

What is the name of the gene responsible for almost all cases of achondroplasia?

FGFR3 Signup and view all the answers

What is a characteristic of monogenic diseases?

They are caused by a single genetic mutation Signup and view all the answers

What is the name of the online database that collects and updates monogenic diseases?

OMIM Signup and view all the answers

What is the characteristic of the FGFR3 gene mutations that cause achondroplasia?

They are specific mutations that cause the condition Signup and view all the answers

What is the term for genetic disorders that are caused by a single genetic mutation?

Monogenic diseases Signup and view all the answers

What is the name of the term that describes the five models of monogenic disease, based on the chromosomal location of the gene locus and the character of the resulting phenotype?

Mendelian inheritance patterns Signup and view all the answers

What is the frequency of cystic fibrosis in white newborns?

1 in 2,500 to 3,500 Signup and view all the answers

What type of mutation causes X-linked dominant disorders?

Mutations in genes on the X chromosome Signup and view all the answers

What is the effect of a mutation in the only copy of the gene in each cell in males with X-linked dominant disorders?

The disorder occurs Signup and view all the answers

What is the name of the disease that is characterized by calcification around joints?

Chondrodysplasia punctata Signup and view all the answers

What is the name of the gene that is most commonly associated with autosomal dominant retinitis pigmentosa?

RHO Signup and view all the answers

How many genes are associated with the autosomal recessive form of retinitis pigmentosa?

At least 35 genes Signup and view all the answers

What is the name of the gene that is most commonly associated with the autosomal recessive form of retinitis pigmentosa?

USH2A Signup and view all the answers

What is the term used to describe retinitis pigmentosa when it occurs by itself?

Nonsyndromic Signup and view all the answers

What is the primary mechanism of mitochondrial disease inheritance?

Maternal inheritance Signup and view all the answers

Which of the following organs is most affected by mitochondrial diseases?

Brain Signup and view all the answers

What is the characteristic of mitochondrial diseases due to nuclear genes?

Affecting only nuclear DNA Signup and view all the answers

What is the term used to describe primary disorders of mitochondrial metabolism affecting oxidative phosphorylation?

Mitochondrial disorder Signup and view all the answers

What is the age of onset for most nuclear genetic mitochondrial disorders?

Adulthood Signup and view all the answers

What is the characteristic of mitochondrial DNA deletions or duplications?

Rearrangements Signup and view all the answers

What is the pattern of inheritance of nuclear gene variants in mitochondrial diseases?

Autosomal recessive, autosomal dominant, or X-linked Signup and view all the answers

What type of genetic disorders typically affect only one organ system and are influenced by a combination of genetic and environmental factors?

Multifactorial disorders Signup and view all the answers

Which type of genetic disorder is characterized by a dominant/recessive pedigree pattern and can affect structural proteins, enzymes, receptors, or transcription factors?

Autosomal dominant disorders Signup and view all the answers

What is the significance of Coenzyme Q10 deficiency in mitochondrial diseases?

It is an example of a nuclear genetic disorder Signup and view all the answers

What is the primary purpose of collecting family history information in the context of genetic disorders?

To establish biological relationships and clarify medical conditions Signup and view all the answers

Which type of genetic disorder is characterized by the involvement of thousands of genes and can affect multiple organ systems at multiple stages in gestation?

Chromosomal disorders Signup and view all the answers

How many generations of family history information should be collected to provide a comprehensive understanding of a patient's genetic background?

3 generations Signup and view all the answers

What type of genetic disorder is typically inherited in a de novo pattern, but can also be inherited in an autosomal dominant or recessive pattern?

Chromosomal disorders Signup and view all the answers

What is the purpose of recording family history information in a pedigree?

To visualize the relationships between family members and their medical conditions Signup and view all the answers

What is the primary factor that determines the expression of a genetic disorder in an individual?

Liability above a threshold Signup and view all the answers

Study Notes

Inheritance of Achondroplasia

Achondroplasia is inherited in an autosomal dominant pattern.
About 80% of people with achondroplasia have average-size parents; these cases result from new mutations in the FGFR3 gene.
In the remaining cases, people with achondroplasia have inherited an altered FGFR3 gene from one or two affected parents.

Autosomal Recessive Disorders

Recessive conditions clinically manifest only when a person has two copies of the mutant allele.
Usually, the parents are unaffected (carriers).

Examples of Autosomal Recessive Diseases

Tay-Sachs: a rare disorder in genetically isolated groups (Jewish populations of North America), characterized by blindness associated with mental retardation, and premature death.
Hemochromatosis
Phenylketonuria
Cystic fibrosis

Case Study: Cystic Fibrosis

Characterized by the buildup of thick, sticky mucus that can damage many of the body's organs.
Common signs and symptoms include progressive damage to the respiratory system and chronic digestive system problems.
It is due to mutations in the CFTR gene, which provides instructions for making a channel that transports chloride ions into and out of cells.

Inheritance of Cystic Fibrosis

It is inherited in an autosomal recessive pattern.

Monogenic Diseases

They are collected and updated in the online version of "Mendelian Inheritance in Man" (OMIM).
There are five models of monogenic disease, based on the chromosomal location of the gene locus and the character of the resulting phenotype:
- Autosomal dominant
- Autosomal recessive
- X-linked dominant
- X-linked recessive
- Y-linked

Autosomal Dominant Disorders

One mutated copy of the gene in each cell is sufficient for a person to be affected by an autosomal dominant disorder.
In some cases, there are new mutations, although usually, an affected person inherits the condition from an affected parent.

Examples of Autosomal Dominant Disorders

Familial hypercholesterolemia
Myotonic dystrophy
Neurofibromatosis I
Huntington disease
Achondroplasia

Case Study: Achondroplasia

A form of short-limbed dwarfism
Patients have average-size trunk, short arms and legs, with particularly short upper arms and thighs, and macrocephaly
Other symptoms include apnea, obesity, and recurrent ear infections
Two specific mutations in the FGFR3 gene are responsible for almost all cases of achondroplasia

X-Linked Dominant Disorders

X-linked dominant disorders are caused by mutations in genes on the X chromosome
In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder
In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder

Examples of X-Linked Dominant Diseases

Chondrodysplasia punctata: calcification around joints
Hypophosphatemic rickets: bone demineralization
Fragile X syndrome: learning disabilities and cognitive impairment
Some forms of retinitis pigmentosa: a degenerative disease of the retina

Case Study: Retinitis Pigmentosa

A group of related eye disorders that cause progressive vision loss
In people with retinitis pigmentosa, vision loss occurs as the light-sensing cells of the retina gradually deteriorate
The signs and symptoms of retinitis pigmentosa are most often limited to vision loss
When the disorder occurs by itself, it is described as nonsyndromic
Mutations in more than 60 genes are known to cause nonsyndromic retinitis pigmentosa

Inheritance of Retinitis Pigmentosa

Mutations in the RHO gene are the most common cause of autosomal dominant retinitis pigmentosa
At least 35 genes have been associated with the autosomal recessive form
The most common of these is USH2A

Prevalence of Disorders

Multifactorial (common): “Environmental” influences act on a genetic predisposition to produce a liability to a disease
Single gene (1% liveborn): Dominant/recessive pedigree patterns (Mendelian inheritance)
Chromosomal (0.6% liveborn): Thousands of genes may be involved

Pedigrees

Why collect family history information?:
- Patient concern
- Clinical feature
- Routine assessment
- Result of screening test
- Opportunistic
What information should you collect?:
- Establish biological relationships
- Clarify the medical conditions that people have
- For each person: full name, date of birth (or age), date of death (or age died), medical information (age at diagnosis)

Mitochondrial Diseases

I. Mitochondrial diseases due to nuclear genes:
- Nuclear genetic disorders of the mitochondrial respiratory chain
- Nuclear genetic disorders associated with multiple mtDNA deletions or mtDNA depletion
- Other disorders (e.g. Coenzyme Q10 deficiency)
II. Mitochondrial diseases due to mutations in mtDNA:
- Rearrangements (deletions and duplications)
- Single-nucleotide variants
- tRNA genes
- rRNA genes
III. Secondary mitochondrial dysfunction in human diseases:
- Ongoing research indicates that mitochondrial dysfunction can be linked to processes such as ageing or neurodegeneration

Clinical Onset

The majority of mtDNA disorders occur in childhood
The majority of nuclear genetic mitochondrial disorders occur in adulthood

Mitochondrial Disease Inheritance Pattern

Mitochondrial DNA variants are transmitted by maternal inheritance (only one case of paternal inheritance described in the literature)
Nuclear gene variants may be inherited in an autosomal recessive, autosomal dominant, or X-linked manner

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Description

Explore the autosomal dominant pattern of inheritance of achondroplasia, including the role of new mutations in the FGFR3 gene and inheritance from affected parents.