Neuro,Mitochondria,Microdeletions Flashcards
-Neuro -Mitochondria -Microdeletions
Alzheimer disease gene/chr mutation.
- APP gene (Amyloid Precursor Protein)
- chr21
Usual (late) onset DZ associated with what gene/allele.
-APOE gene (E4 allele)
Pick disease (frontotemporal dementia with Parkinsoniasm) gene mutation and protein.
- MAPT gene
- Microtubule Associated Protein Tau
Familial cases of Parkinson disease and Lewy body disease spectrum are ass. w/ anomalies in which genes?
PARK1 through PARK8
Huntington Disease genetics (inheritance/trinucloetide repeat/gene/chr).
- Autosomal Dominant
- CAG repeats
- HTT gene on chr4p
In Huntington Dz what number of repeats is considered a Premutation?
28-35
<28 is normal phenotype
In Huntington Dz what number of repeats is associated with disease?
> 40
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarctions and Leukoencephalopathy (CADASIL) gene mutation.
NOTCH3
Histology of CADASIL.
Vessels with granular eosinophilic medial deposits.
affected vessels may be found in skin
Autosomal Dominant disorder caused by duplication of a 1.5Mb region of DNA on chr17 containing the PMP22 gene.
Charcot-Marie-Tooth
What does Charcot-Marie-Tooth affect and what are the histological findings?
- Sensory and Motor neurons
- Onion Bulb formation
Autosomal Recessive disease associated with Lower Motor Neuron deficits.
Spinal Muscular Atrophy (SMA)
What is the most severe form of Spinal Muscular Atrophy?
SMA type I
-Werdnig-Hoffman disease
What mutation is involved in all cases of Spinal Muscular Atrophy?
SMN1 gene (survival motor neuron 1)
Dystrophinopathies (Duchenne and Becker) gene/chr/inheritance.
- DMD gene on Xp21.2
- X linked recessive (1/3 are sporadic)
Myotonic Muscular Dystrophy genetics.
Autosomal Dominant
-Trinucleotide Repeat Disorder
Genetics of Malignant Hyperthermia (MH).
RYR1 calcium channel defect
What is the 1st sign of Malignant Hyperthermia?
Hypercarbia while under anasthesia
Mitochondrial disorders:
-Typical findings
- Optalmoplegia
- Ptosis
- Retinopathy
- Skeletal Myopathy
- Cardiomyopathy
- Sensorineural Deafness
- Encephalopathy
Screening tests for Mitochondrial disorders.
- Lactic Acid (plasma or CSF)
- Ketones
- Acylcarnitines
- Urinary organic acids
Characteristic muscle biopsy findings in Mitochondrial disorders.
- Ragged red fibers (trichrome)
- “Parking Lot” inclusions (EM)
Two syndromes caused by major structural defects–gross deletions or large rearrangements–in mtDNA.
- Kearns-Sayre syndrome
- Pearson syndrome
Syndrome characterized by progressive neurologic deterioration after initially normal development.
MELAS
-Mitochondrial Encephalopathy with Lactic Acidosis and Strokelike episodes
MELAS genetics.
MT-TLI gene point mutations
-located within the mtDNA
Microdeletion syndrome:
- Abnormal cry, microcephaly, MR
Cri du chat (5p15)
Microdeletion syndrome:
- Hyperphagia, obesity, hypogonadism, mild MR
Prader-Willi (Paternal; 15q11)
Microdeletion syndrome:
- Anosmia, hypogonadism
Kallman (Xp22.3)
Microdeletion syndrome:
-Hyperactivity, inappropriate laughter, aphasia, ataxia, MR, seizures
Angelman (Maternal; 15p11)
Microdeletion syndrome:
-CHARGE sequence manifestations
- Coloboma
- Cardiac malformation
- Choanal atresia
- Genital hypoplasia
- Deafness
- MR
Microdeletion syndrome Abberations:
- DiGeorge, Catch 22, CHARGE, velo-cardiofacial
22q11.2
Microdeletion syndrome Abberations:
- Cri du chat
5p15
Microdeletion syndrome Abberations:
- Kallman
Xp22.3
Microdeletion syndrome Abberations:
- Prader-Willi
15q11.2 (PATERNAL)
Microdeletion syndrome Abberations:
- Angelman
15q11.2 (MATERNAL)
Microdeletion syndrome Abberations:
- Williams syndrome (Elfinlike facies, infantile hypercalcemia)
7q11
