1
Q
What is an intron?
A
The DNA sequence of a gene located between 2 exons that is transcribed into messenger RNA (mRNA) but spliced out during the formation of mature mRNA.
Function is unknown.
2
Q
What is an exon?
A
The DNA sequence of a gene located between 2 introns that is transcribed into mRNA and retained after the primary mRNA is spliced.
It is the ultimate gene product.
3
Q
Define genome.
A
The entire DNA of an individual, which contains introns and exons.
4
Q
What is the exome?
A
The coding region of the genome, approximately 1.5% of the genome, which contains only exons.
5
Q
True or False: Introns are retained in mature mRNA.
A
False.
6
Q
Fill in the blank: The _____ is the ultimate gene product.
A
[exon]
7
Q
How much of the genome does the exome represent?
A
Approximately 1.5%.
8
Q
What is the primary role of exons in mRNA?
A
They are transcribed into mRNA and retained after splicing.
9
Q
What happens to introns during mRNA processing?
A
They are spliced out.
10
Q
What is a microarray?
A
Molecular fragments of DNA or protein are attached to a glass or plastic slide in a specific order.
11
Q
What are the three clinical uses of microarrays?
A
- Comparative Genomic Hybridization (CGH) microarray
- Microarray expression analysis
- Mutation microarray analysis
12
Q
What does the Comparative Genomic Hybridization (CGH) microarray attempt to identify?
A
The number of copies of a particular gene to determine if a genomic gain or loss has occurred.
13
Q
What does microarray expression analysis determine?
A
If a gene is over or underexpressed.
14
Q
What is the purpose of mutation microarray analysis?
A
To identify mutations or polymorphisms in a gene.
15
Q
What is targeted mutation analysis?
A
Detection of known sequence or triplet repeat expansion.
16
Q
What is methylation analysis used for?
A
Detection of imprinting disorder.
17
Q
What does whole exome sequencing determine?
A
The nucleotide sequence of all protein-coding sites (~1-2% of entire human genome).
18
Q
When is whole exome sequencing particularly useful?
A
If a patient presents without a clear reason for a specific phenotype that may be due to different genes.
19
Q
What percentage of exons does whole exome sequencing miss?
A
About 3-5% of exons.
20
Q
What is a Point Mutation?
A
1 base pair is substituted for another
21
Q
What characterizes a Frameshift Mutation?
A
Insertion or deletion of a nucleotide
22
Q
What is a Silent Mutation?
A
Mutated DNA with no change in amino acid sequence
23
Q
What is a Missense Mutation?
A
Mutated DNA resulting in a different amino acid
24
Q
What is a Nonsense Mutation?
A
Mutated DNA that creates a STOP codon in mRNA
25
What is the effect of a Nonsense Mutation on protein function?
Results in a nonfunctional protein
26
What occurs during an Insertion Mutation?
Inserted mutated RNA leads to a change in amino acid sequence
27
What happens during a Deletion Mutation?
Deleted nucleotide in mutated RNA changes amino acid sequence
28
What is a Splice Site Mutation?
Insertion or deletion of nucleotides that affects splicing
29
True or False: A Silent Mutation changes the protein produced.
False
30
Fill in the blank: A _______ Mutation results in a STOP codon.
Nonsense
31
Fill in the blank: A _______ Mutation leads to a different amino acid sequence.
Missense
32
What percentage of genes may be expressed differently based on parental inheritance?
Approximately 1%
## Footnote
This refers to genomic imprinting where gene expression is affected by whether the gene is inherited from the mother or father.
33
What is maternal imprinting?
Silencing of maternally derived gene
## Footnote
Maternal imprinting affects gene expression based on maternal inheritance.
34
What is paternal imprinting?
Silencing of paternally derived gene
## Footnote
Paternal imprinting affects gene expression based on paternal inheritance.
35
Name one human syndrome resulting from genomic imprinting.
Prader-Willi syndrome
## Footnote
Other syndromes include Angelman syndrome, Beckwith-Wiedemann, Russell-Silver, and more.
36
What happens if a deletion in chromosome 15 is inherited from the father?
Offspring will have Prader-Willi syndrome
## Footnote
This is due to paternal imprinting affecting the expression of genes on that chromosome.
37
What happens if a deletion in chromosome 15 is inherited from the mother?
Offspring will develop Angelman syndrome
## Footnote
This is due to maternal imprinting affecting the expression of genes on that chromosome.
38
How many human syndromes are currently known to result from genomic imprinting?
9 syndromes
## Footnote
These include Prader-Willi syndrome, Angelman syndrome, Beckwith-Wiedemann, and others.
39
What is uniparental disomy?
Inheritance of 2 copies of a chromosome from one parent and none from the other
## Footnote
This can cause issues if normal gene function requires one copy from each parent.
40
What can uniparental disomy lead to?
Prader-Willi syndrome and Angelman syndrome
## Footnote
The outcome depends on which chromosome is duplicated.
41
Fill in the blank: A paternal deletion of the 15q region results in _______.
Prader-Willi syndrome
42
Fill in the blank: A maternal deletion of the 15q region results in _______.
Angelman syndrome
43
What may occur following the attempted self-correction of a trisomic chromosome?
Elimination of one chromosome leading to 2 copies from the same parent
## Footnote
This can result in uniparental disomy.
44
True or False: Maternal hypomethylation syndromes are one of the syndromes associated with genomic imprinting.
True
45
What is the significance of the 15q region in Prader-Willi and Angelman syndromes?
It is critical for normal gene expression depending on parental inheritance
## Footnote
Deletions or duplications in this region lead to the respective syndromes.
46
What type of genetic disorder is Carpenter syndrome?
Autosomal recessive
## Footnote
Carpenter syndrome is characterized by various physical anomalies and health issues.
47
What cardiac defects are associated with Carpenter syndrome?
* Patent ductus arteriosus
* Ventricular septal defect
* Atrial septal defect
* Pulmonary stenosis
* Tetralogy of Fallot
* Transposition of the great arteries
## Footnote
Cardiac issues occur in approximately 50% of cases.
48
What extremity anomalies are seen in Carpenter syndrome?
* Polydactyly
* Syndactyly (feet)
* Clinodactyly
## Footnote
These anomalies affect the formation of fingers and toes.
49
List some facial characteristics of Carpenter syndrome.
* Lateral displacement of inner canthus
* Shallow supraorbital ridges
* Flat nasal bridge
* Corneal opacity
* Optic atrophy
* Low-set and malformed ears
* Hypoplastic mandible and/or maxilla
* High-arched palate
## Footnote
These features contribute to the distinct facial appearance associated with the syndrome.
50
What neurological features are associated with Carpenter syndrome?
* Brachycephaly
* Mental deficiency
## Footnote
Neurological issues can vary in severity among affected individuals.
51
What are some other clinical features of Carpenter syndrome?
* Failure to thrive
* Hypogenitalia
* Umbilical hernia
* Omphalocele
## Footnote
These features can impact overall health and development.
52
What type of genetic disorder is Ellis-van Creveld syndrome?
Autosomal recessive, chondroectodermal dysplasia
## Footnote
This syndrome affects the development of cartilage and ectodermal tissues.
53
What cardiac issues are present in Ellis-van Creveld syndrome?
* Single atrium
* Atrial septal defect
## Footnote
Cardiac involvement occurs in approximately 60% of cases.
54
What extremity features are associated with Ellis-van Creveld syndrome?
* Short distal extremities
* Polydactyly (more common in fingers than toes)
* Nail hypoplasia
* Short stature
## Footnote
These features can affect mobility and physical appearance.
55
What facial characteristics are noted in Ellis-van Creveld syndrome?
* Delayed teeth eruption
* Short upper lip
## Footnote
These features may influence dental health and facial aesthetics.
56
What are some other clinical outcomes associated with Ellis-van Creveld syndrome?
* Intrauterine growth restriction
* Narrow thorax
* Typically normal intelligence
## Footnote
Growth and development can be affected, but cognitive function often remains intact.
57
What is the mortality rate during infancy for Ellis-van Creveld syndrome and its primary cause?
50% mortality due to cardiorespiratory difficulties
## Footnote
Infants may face significant health challenges that can lead to early mortality.
58
What is the etiology of Fanconi pancytopenia syndrome?
Autosomal recessive
## Footnote
Increased number of chromosomal breaks in lymphocytes and amniotic fluid cells.
59
What are the clinical features of hyperpigmentation in Fanconi pancytopenia syndrome?
Increases with age, especially involving groin, axilla, and trunk.
60
What are the extremity abnormalities associated with Fanconi pancytopenia syndrome?
Radial hypoplasia, thumb hypoplasia, short stature.
61
What facial abnormalities are present in Fanconi pancytopenia syndrome?
Ptosis, nystagmus, microphthalmus, strabismus.
62
What genitourinary abnormalities are found in Fanconi pancytopenia syndrome?
Renal and urinary tract abnormalities (35%), hypospadias, small genitalia.
63
What is the hematological presentation of Fanconi pancytopenia syndrome?
Pancytopenia (presents at ~7 years of age but may occur during infancy).
64
What neurological issues may arise in Fanconi pancytopenia syndrome?
Microcephaly, mental deficiency (25%).
65
What are other clinical features associated with Fanconi pancytopenia syndrome?
Intrauterine growth restriction, increased risk of respiratory infections, may have cardiac defect.
66
What is the mortality rate associated with Fanconi pancytopenia syndrome?
~35% mortality because of hematological abnormalities, increased risk of acute myelogenous leukemia.
67
What is the etiology of Meckel-Gruber syndrome?
Autosomal recessive, locus mapped to 17q21-q24.
68
What cardiac defects are associated with Meckel-Gruber syndrome?
Atrial septal defect, ventricular septal defect, patent ductus arteriosus, coarctation of the aorta, pulmonary stenosis.
69
What extremity abnormalities are found in Meckel-Gruber syndrome?
Polydactyly (usually postaxial).
70
What facial features are associated with Meckel-Gruber syndrome?
Microphthalmia, cleft palate, micrognathia, ear anomalies.
71
What genitourinary issues are seen in Meckel-Gruber syndrome?
Cryptorchidism, incomplete genitalia.
72
What neurological abnormalities can occur in Meckel-Gruber syndrome?
Occipital encephalocele, microcephaly, cerebral and cerebellar hypoplasia, hydrocephaly, absence of corpus callosum, septum pellucidum, or olfactory lobes/tract.
73
What renal condition is associated with Meckel-Gruber syndrome?
Cystic dysplastic kidneys.
74
What other complications may arise in Meckel-Gruber syndrome?
Bile duct proliferation, hepatic cysts.
75
What prenatal diagnosis marker is elevated if encephalocele is present in Meckel-Gruber syndrome?
Elevated alpha fetoprotein.
76
What does the outcome of Meckel-Gruber syndrome depend on?
Severity of illness.
77
What is a characteristic feature of Meckel-Gruber syndrome compared to Amniotic Band syndrome?
Presence of cephalocele.
78
True or False: Microphthalmia is a feature of both Meckel-Gruber syndrome and Amniotic Band syndrome.
True.
79
Fill in the blank: Meckel-Gruber syndrome can present with _______ defects.
Cardiac.
80
What is the distinguishing feature of polydactyly in Meckel-Gruber syndrome?
Usually postaxial.
81
What are the neurological anomalies associated with Walker-Warburg syndrome?
CNS anomalies (ventriculomegaly, midline abnormalities, lissencephaly).
82
Low AFP, Low Estriol, high hCG, high Inhibin A =
Trisomy 21
83
Low AFP, Low Estriol, Very high hCG, very high Inhibin A =
Turner syndrome
84
Increased AFP, normal estriol, Inhibin & hCG =
Patau Syndrome
85
Post natal chorioretinal lacunae is pathognomonic for…
Aicardi syndrome
86
female patient, agenesis of corpus callosum, intractable seizures, and ocular findings are suggestive of…
Aicardi syndrome
87
facial features (broad forehead, bitemporal narrowing, bulbous nasal tip, flat philtrum, wide mouth, prominent earlobes), pulmonary valvar stenosis, and hearing loss,
Williams syndrome
88
Which syndrome? congenital aplasia cutis and terminal transverse limb anomalies, genetic mutations affecting the GTPase pathway during gestation, cardiac defects, pulmonary HTN
Adams Oliver syndrome
89
Characterized by multiple areas of fibrous dysplasia of the long bones (may include ribs and spine), irregular brown pigmentation (sacrum, buttocks, upper spine), hyperthyroidism, hyperparathyroidism, pituitary adenomas.
McCune-Albright Syndrome
90
How many CTG repeat copies causes severe phenotype in myotonic dystrophy?
>2,snip000 copies. Number of repeats directly related to severity and age of onset of disease. Largest expansions appear to occur mainly from maternal transmission. 5-30 copies = normal. Mom may have milder phenotype.
91
What are the four stages of incontinentia pigmenti and how is it inherited?
Blistering, verrucous, swirling macular hyperpigmentation, linear hypopigmentation. X linked dominant disorder. Mutations in NEMO gene, lethal in males.
92
How is Cornelia de Lange syndrome inherited?
AD and x-linked.
93
When do you order a gene panel?
phenotype targeted, cover multiple genes, avoid overwhelming VUS, cost effective. Cons - gene selection and panel too narrow, miss new gene information.
94
When do you order exome/genome sequencing?
Severe and unique phenotype without good explanation (life threatening presentation), extreme heterogeneity and de novo changes (autism, intellectual disability, seizures), 2 or more likely unrelated phenotypes in 1 patient. Strong family history. Exome = 1-2% of the genes that code for proteins, Genome = all introns, promoter, regulatory regions + exome + mitochondrial disorders.
95
What is the gene mutation found in 60% of CHARGE cases?
CHD7
96
What testing can suggest Fanconi anemia?
diepoxybutane testing (DEB), positive is chromosome breakage, then send gene panel for fanconi anemia
97
How is Beckwith-Wiedemann syndrome inherited?
DMR2 loss of methylation (50%), paternal uniparental disomy (20%)
98
Respiratory distress, ptosis, bilateral facial paralysis, talipes equinovarus, deficits along the 6th and 7th cranial nerves, ophthalmoplegia, syndactyly. The facial immobility secondary to the 7th nerve involvement causes upper airway obstruction and difficulties in feeding - Name the syndrome or sequence
Mobius syndrome or sequence, sporadic inheritance, PLXND1, REB3L and TUBB3 genes.
99
Infant with short stature, moderate to severe intellectural disability, distinctive facial features, broad thumbs, broad first toes, eye abnormalities, heart abnormalities, kidney abnormalities, dental problems and obesity - Name syndrome.
Rubinstein-taybi syndrome
100
Enlarged kidneys with numerous fluid-filled cysts, occipital encephalocele, presence of extra fingers and toes, fibrosis of the liver, mutation of at least one of eight genes, proteins produced from these genes lead to an abnormality in the function of the cilia - name of the syndrome?
Meckel-Gruber syndrome
101
What is the gene defect with thanatophoric dysplasia and it's inheritance pattern?
extracellular domain or intracellular tyrosine kinase domain of the fibroblast growth factor receptor gene 3, AD
102
What is the gene defect with achondroplasia?
transmembrane domain of the FGF receptor gene 3, AD inheritance
103
Most common cardiac defect for noonan syndrome?
Dysplastic pulmonary valve. AD with wide variable expression.
104
What is all the same between Apert, Crouzon and Muenke syndromes?
All AD, all hypertelorism, all craniosynostosis, all proptosis, all mutation in a fibroblast growth factor receptor gene
105
What percentage of craniosynostosis are non-syndromic?
70%
106
Which type of osteogenesis imperfecta is the most severe?
Type 2, usually die. Most severe that can live is type 3.
107
Which disorders are x-linked dominant?
incontinentia pigmentosa, fragile X syndrome, Aicardi syndrome, vitamin D-resistant rickets
108
Which test separates proteins based on size and charge and then uses probe to find protein modifications?
Eastern analysis
109
Which test hybridizes a labeled DNA probe to digested RNA?
Northern analysis
110
Which test hybridizes a labeled DNA probe to digested DNA?
Southern analysis
111
Which test separates proteins based on size and charge and then uses an antibody probe to identify a specific protein?
Western analysis
112
What is a microarray able to detect?
Microdeletions, most unbalanced translocations, most aneuploidies
Unable to detect tiny microdeletions in a single gene (Fragile X), balanced translocations (robertsonian translocation) or point mutations (sickle cell)
113
Name the syndrome - small triangular faces, micrognathia, frontal bossing, skeletal asymmetry.
Russell-Silver syndrome
114
Name the syndrome - lower eyelid coloboma, down-slanting palpebral fissures, mandibular hypoplasia, dysmorphic ears, hearing loss.
Treacher Collins
115
A disorder that has increased frequency in older fathers:
Achrondroplasia
116
Examples of AR inheritance?
Sickle cell anemia, CF, most inborn errors of metabolism
117
Which IEM are x-linked not AR?
OTC Deficiency (most common urea cycle defect, bad in boys), X-linked ALD, Hunter syndrome
118
What is the **percentage gain of methylation** on chromosome 11 maternal for Beckwith Wiedemann inheritance?
5%
119
What is the loss of methylation of maternal chromosome 11 inheritance pattern for beckwith Wiedemann?
50%
120
List the **syndromes** associated with port wine stains.
* Sturge-Weber
* Klippel-Trenaunay-Weber
* Beckwith-Wiedemann
* Cobb syndrome
## Footnote
85% are unilateral
121
What does **Aplasia cutis congenita** involve? (Layers of skin)
Epidermis and dermis
## Footnote
The benign form is autosomal dominant and lesions will re-epithelialize over several months.
122
Aplasia cutis congenita can be associated with chromosomal abnormalities such as __________.
trisomy 13 or 4p-syndrome
## Footnote
These chromosomal abnormalities can occur alongside aplasia cutis congenita.
123
What is a **sebaceous nevus** characterized by?
Isolated oral or linear waxy plaque with cobblestone appearance
## Footnote
This describes the physical characteristics of a sebaceous nevus.
124
What type of mutation is associated with **Coloboma**?
Autosomal dominant mutation in CHD7
## Footnote
This mutation is linked to the development of coloboma.
125
What are the **major defects** associated with CHARGE?
* coloboma
* choanal atresia
* ear anomalies
## Footnote
These defects are classified as major criteria in the context of CHARGE.
126
What are the **minor criteria** for CHARGE?
* heart defect
Renal anomalies
Growth restriction
Genital hypoplasia
127
What is the **Collodion Membrane** associated with?
Thickened stratum corneum, swells from amniotic/nid exposure
## Footnote
This condition is related to skin development issues.
128
Define **ectropion**.
Eversion of lower eyelids
## Footnote
This condition can lead to exposure of the inner eyelid.
129
Define **eclabion**.
Eversion of lips
## Footnote
This condition can affect the appearance and function of the mouth.
130
What does **VACTERL Association** include?
* Vertebral anomalies (70%)
* Anal atresia (80%)
* Cardiac anomalies (50%)
* Tracheoesophageal fistula (TEF) (70%)
* Renal anomalies (53%)
* Limb dysplasia (65%)
## Footnote
This association refers to a group of congenital anomalies.
131
What is the primary cause of **Trisomy 21**?
95% result from nondisjunction, 47 chromosomes
## Footnote
Other causes include 3-4% unbalanced translocation and 1-2% mosaic trisomy (milder form).
132
What is the genetic inheritance pattern of **Apert syndrome**?
Autosomal dominant
## Footnote
This syndrome is caused by a mutation in the fibroblast growth factor receptor.
133
Where are **Ebstein pearls** located?
On the hard palate
## Footnote
These are small cysts that can appear in newborns.
134
What are **dysostoses**?
Malformations of bones
## Footnote
Dysostoses result from abnormalities in mature mRNA.
135
What is the purpose of **Southern analysis**?
To analyze DNA by digesting it and exposing it to a DNA probe
## Footnote
This method involves hybridization of labeled DNA probe to digested DNA fragments.
136
What does **Western analysis** involve?
Separation of proteins based on size
## Footnote
Proteins are separated and then probed for detection.
137
What is a **dot blot** used for?
To amplify DNA in the presence of known mutations
## Footnote
This technique applies to a membrane for further analysis.
138
What can **FISH** be used for?
* Trisomies
* Prader-Willi syndrome
* Angelman syndrome
* Cri du chat syndrome
* DiGeorge syndrome
## Footnote
FISH (Fluorescence In Situ Hybridization) is a technique used for identifying chromosomal abnormalities.
NeoBoardReview
flashcards
Decks in class (15)
# Cards
