Disease Inheritance Chromosom Gene Brief MOA Symptoms Treatment Topic

e
Fabry Disease X-linked X GLA Malproduction of Angokeratoma Recombinant Single Gene
Recessive alpha s, Kidney alpha- Disorders
galactosidase Disease, Galactosidase
resulting in Hypohidrosis infusions
substrate
accumulation
Noonan Syndrome Autosomal Most Most common, Not described Expressionless, None described, Single Gene
dominant with commonly PTPN11 Wispy hair, but WES can be Disorders
variable on 12 broad webbed used to detect
expression neck where mutation is
PKU Autosomal 12 PAH 98%, deficiency in Mental Low Phe diet, Allelic
recessive Phe hydroxylase, impairment, tetrahydrobiopter heterogeneit
(affected 2% are 2/2 a delay, seizures, in therapy y, locus
individuals are tetrahydrobiopter musty odor, heterogenity
compound in deficiency microcephaly
heterozygotes
showing allelic
heterogeneity
)
Tay Sachs/Sandhoff Autosomal 15 Hexosamindase A No cleaving of Neurological – No effective Locus
disease Recessive (Tay Sachs); GM2 ganglioside, motor treatment heterogeneit
Hexosaminidase B causes substrate weakness, y between
(Sandhoff) accumulation cherry red spot hexA/B
in eye,
deterioration
after 10-12
months
Mucopolysaccharido Autosomal Occupy Many; all involved Build up of They vary in None listed Locus
sis disorders (Hurler, Recessive many in different substrate due to severity, Hurler heterogeneit
synthesis of enzyme deficiency is most y in
Schele, Hunter, glycosaminoglyca dangerous Sanfilippo
Sanfilippo A/B) ns causing death syndromes,
before age 10, clinical or
most cause phenotypic
intellectual heterogeneit
disability and y in that all of
slow these
progression, diseases
but those with come about
no intellectual as differing
disability levels of
typicaclly just enzyme
show activities
dysmorphic
phenotype
Tuberous Sclerosis Autosomal 9 TSC1/2 TSC1/2 inhibit Cortical tubers, Rapamycin; Variation of
Dominant mTOR, an infantile inhibits mTOR in two-hit
inhibitor of cell spasms, an analogous hypothesis:
cycle progresson. persistent rash fashion to TSC1/2 2/3 of cases
Lack of mTOR are new
inhibition leads to mutations
rapid growth of resulting in
benign tubers the dominant
allele
Spinal Muscular Autosomal 5 SMN1 Loss of function in Loss of motor Spinraza; I don’t really
Atrophy Recessive SMN1 due to loss neurons in antisense know how it
of exon 7/8. spinal cord oligonucleotide relates to
Variability in resulting in that binds, everything
phenotype is due muscle activates splice else if I’m
to residual weakness and site in SMN2, being honest
function of SMN2, atrophy allowing for
nearly identical creation of useful
upstream exon protein
 that has lower
rates of
translation
Osteogenesis Most of the 9 COL1A1/2, Depending on Blue sclerae, Bisphosphonate Probably
Imperfecta time, LEPRE1 or CRTAP severity, different fracturing easy, locus
autosomal for recessive forms of short – heterogeneit
dominant; variant unassembled perinatal y between
rarely, procollagen lethality and the lethal
autosomal chains have skeletal variant types,
recessive mutations causing deformity in phenotypic
which can improper collagen more extreme heterogeneit
produce lethal fibril formation variants y between
variant others
(autosomal
dominant via
new
mutations)
Neurofibromatosis 1 Autosomal Not on slide Not on slide Non tumor Spectrum – No treatment Two-Hit
Dominant phenotype: anywhere from Hypothesis
heterozygotes café-au-lait
Tumor spots to
phenotype: neurofibroma
occurs via two growth
hit hypothesis
mechanism to
inactivate
tumor
suppressor
gene
 Phenotypes
tend to evolve
over time
Fragile X Syndrome X-linked X FMR1 1. Shows Premutation – None listed Trinucleotide
dominant anticipation – ovarian failure repeat
nucleotide and ataxia disorders
 Trinucleotid repeat Full expansion
e Repeat of expands over – mental
CGG generation disability,
(more macroorchidis
unstable from m, long
maternal face/jaw
passage)
2. Expansions
over 200
repeats cause
no production
of FMR1
3. Full disease:
no FMR
protein,
upregulation
of protein
translation at
synapse, cell
wants it to be
just mRNA
there, causes
neurological
problems
4. Premutation –
FMR protein
at abnormal
levels, which
means
abnormal
amount of
 mRNA at
synapse
Charcot-Marie-Tooth Autosomal 17 PMP22 Duplication of Neuropathies None listed Duplication
Dominant PMP22 gene characterized
by pes cavus,
distal muscle
weakness, foot
drop
Myotonic Dystrophy Autosomal 19 DMPK Not listed Anticipation – None listed Trinucleotide
1 Dominant gets worse repeat
 Trinucleotid throughout disorder
e repeat of generations –
CTG can be from
cataracts at old
age to facial
weakness and
myotonia to
perinatal death
Friedrich Ataxia Autosomal 9 Frataxin Not listed Hypertrophic None listed Trinucleotide
Recessive cardiomyopath repeat
 Trinucleotid y, ataxic gait, disorder
e repeat of diabetes
GAA
Huntington Disease Autosomal 4 Huntingtin Not listed Chorea, mental Not listed Trinucleotide
Dominant disability repeat
 Trinucleotid disorder
e repeat of
CAG