Question

A 32-year-old Caucasian man underwent testing for Huntington’s Disease. The patient was a lively and talkative child who completed high school with As and Bs and college with poor grades. At age 22 he became quiet and non-conversant. At age 24 he began work as a cook/dishwasher and displayed noticeable un-coordination. At age 28 he developed dysarthria, dysphagia, stiffness, slow ataxic gait, and dementia. There was no history of schizophrenia or depression and the neurological review of systems was negative. Both parents were in their late 60s and in excellent health, without signs of dementia. There was no history of any neurodegenerative disease and he had three sisters, aged 35-37, all in good health.

Laboratory Results:

Creatine phosphokinase: Normal

Vitamin E: Normal

Lactate: Normal

Pyruvate: Normal

Imaging Results:

MRI: Generalized, cerebral and cerebellar atrophy

​​Very mall caudate nuclei

HIstology Results:

Skin biopsy: Normal mitochondria

Bone Marrow and Enzyme Screen:

Human Granulocyte-Macrophage: Normal

Metachromatic Leukodystrophy: Normal

Krabbe’s disease: Normal

Physical examination:

Mini-mental status exam: 20/26

Cranial nerve exam: decreased upgaze, saccadic extraocular eye movement, dysarthria and hyperactive gag reflex

Strength: Normal

Gait: wide-based and ataxic

Molecular Test Results:

Diagnostic HTT molecular test for patient:

​​​1 band representing 23 CAG repeats

​​​1 band representing 49 CAG repeats

HTT molecular test for father:

​​​1 band representing 20 CAG repeats

​​​1 band representing 37 CAG repeats

HTT molecular test for mother:

​​​1 band representing 17 CAG repeats

Predictive HTT molecular test for sister:

​​​1 band representing 17 CAG repeats

​​​1 band representing 20 CAG repeats

Why did the patient show phenotypic traits while his parents and sisters did not?

If this patient has a child with an unaffected female, what are the chances that the child will have HD?

Answer 1

Huntington's disease caused by an inherited defect in a single gene, it is an autosomal dominant disorder that means the person needs only one copy of the defective gene to have this disorder. Gene mutation does not carry mutations associated with HT disorder.irrgular expansions of glutamine repeats develop this disease. HD is phenotypically characterized by progressive motor, cognitive, and physical abnormalities.so these phenotypic traits occur for this patient while his parents and sisters did not.
when a parent has HD there is a 50% of each child has a chance of inheriting the copy of chromosome 4 that carry
the HD mutations. if the child does not inherit the HD mutations then the child will not develop the disease and they will not pass the disease to subsequent generations.