X linked and mitochondrial inheritance Flashcards
X chromosome inactivation occurs when?
1st week of embryogenesis
Nonrandom vs skewed x chromosome inactivation
Nonrandom- when structurally abnormal x chromosome present, more of normal xs are turned on usually
Skewed- observed when female shows signs of x linked recessive condition
X linked dominant conditions (4)
Hypophosphatemic Rickets
Fragile X syndrome
Charcot Marie Tooth
Rett Syndrome
Clinical manifestation of hypophosphatemic rickets (3)
Hypophosphatemia
short stature
bone deformity
Mutation leading to hypophosphatemic rickets occurs on the ____ gene which regulates _____. This inhibits ______
Gene: PHEX
Regulates fibroblast growth factor
Inhibits the kidneys ability to reabsorb phosphate into the blood stream
Fragile X syndrome gene
FMR1
Fragile X syndrome exhibits ______ and ________.
Anticipation
Maternal transmission bias
Clinical manifestations of Fragile X (6)
intellectual disabilities large ears, long face, macroorchidism autistic behavior social anxiety hand flapping/biting agression
Other conditions associated with FMR1
Fragile X Associated Tremor Ataxia (FXTAS)
FMR1- related primary ovarian insufficiency
CGG repeats fragile X: grey zone, premutation, and full mutation
46-65: Grey
56-200: Premutation
>200: Full mutation
Mutation rate of Rett syndrome
95%
Clinical Manifestations of Rett syndrome (6)
Loss of normal movement and coordination Acquired microcephaly Loss of communication skills Failure to thrive Seizures Abnormal hand movements
Rett syndrome gene mutation
MECP2
MECP2 gene (Rett) encodes for what protein?
Methyl CpG binding protein
Essential for the normal function of nerve cells
X-linked Recessive Disorders (4)
Lesch-Nyhan Syndrome
Hemophilia A
Fabry’s disease
Dystrophonpathies
Clinical Manifestations of Lesch-Nyhan (4)
Cerebral palsy
Cognitive and behavioral disturbances
Overproduction of uric acid
Self injury
Gene mutation Lesch Nyhan
HPRT1
Hypoxthine phosphoribosyltransferase
recycling of purines
Gene mutation for Duchenne and Becker Muscular dystrophies
DMD
encoding for dystrophin
Location of DMD on chromosome
Xp21-21.1
Clinical Manifestations of Duchenne (8)
Progressive muscular weakness proximal > distal Calf hypertrophy Dilated cardiomyopathy CK levels 10x normal Onset before the age of 5 Wheelchair bound before 13 Death in their 30’s Absence of Dystrophin
Clinical manifestations of Becker (7)
Progressive muscular weakness proximal > distal
Dilated cardiomyopathy
CK levels 5x normal
Later onset
Wheelchair bound after 16
Death in their 40’s
Abnormal quantity or quality of Dystrophin
DMD-associated DCM
Dilated cardiomyopathy presenting between 20-40 years of age
Early death
No skeletal muscle involvement
No Dystrophin in the myocardium
What percentage of Hemophilia A carrier females are affected?
10%
Clinical manifestations of Hemophilia A
Blood disorder where blood fails to clot appropriately due to a deficiency of Factor VIII
Spontaneous bleeds into joints, muscles or intracranial
Excessive bruising
Prolonged bleeding after injury or incision
Delayed wound healing
Gene mutation of Hemophilia A
F8
Encoding for Factor VIII
Chromosome location for Hemophilia A mutation
Xq28
22A inversion causes 50%
How many genes does mtDNA encode?
37
Mitochondrial DNA mutation diseases (4)
Kearnes-Sayre
MELAS
MERFF
Leber Hereditary Optic Neuropathy
Clinical manifestations of Kearnes-Sayre (7)
Triad: Pigmentary Retinopathy Progressive External Ophthalmoplegia And onset before age 20y Cardiac conduction defects Ataxia Deafness Kidney problems
MELAS and MERFF have a high or low new mutation?
Low
Clinical manifestations of MELAS (5)
Starts between age 2 & 10 y Muscle weakness Seizures Repetitive stroke-like episodes Elevated lactic acidosis
Most common gene mutation in MELAS
MT-TL1 (80%)
MERRF clinical manifestations (5)
Muscle symptoms Seizures Ataxia Dementia Ragged-red fibers
Gene mutation for MERFF
MT-TK
Clinical manifestations of Leber hereditary Optic Neuropathy
Bilateral subacute vision failure
Occurs during young adulthood
