NEUROMUSCULAR DISORDERS Flashcards
5 yo adopted boy with tip toe walking, Gowers sign, inability to jump, calf hypertrophy and CK 75 times normal. Intelligence appears normal despite language barrier in school. Which of the following would most likely be ordered as the next step in the workup for diagnosis?
A. Deletion/duplication analysis of the DMD gene
B. NGS of all genes related to muscular dystrophy
C. Sequence analysis of the DMD gene
D. Skeletal muscle biopsy for Western blot studies of dystrophin
E. Skeletal muscle biopsy for dystrophin IHC
F. None of the above
A. Deletion/duplication analysis of the DMD gene
5 yo adopted boy with tip toe walking, Gowers sign, inability to jump, calf hypertrophy and CK 75 times normal. Intelligence appears normal despite language barrier in school. Which one of the following molecular assays would likely provide the most appropriate first-tier molecular workup for this patient?
A. Multiplex ligation-dependent probe amplification
B. NGS
C. Sanger sequencing
D. TaqMan genotype assays
E. None of the above
A. Multiplex ligation-dependent probe amplification
A patient was suspected to have DMD but a deletion/duplication study for the DMG gene was negative. What would most likely be used as the next step in the molecular workup to rule out DMD in this patient?
A. Multiplex ligation-dependent probe amplification
B. Sanger sequencing analysis
C. TaqMan genotype assays
D. Quantitative PCR
E. None of the above
B. Sanger sequencing analysis
4 yo boy with delayed walking, Gowers sign, CK 26,000 and muscle biopsy showing fatty replacement with fibrosis and myopathic features. Western blot was abnormal. A 2-year old sister was in good health. How frequently do DMD patients have inherited pathogenic variants?
A. <1%
B. 25%
C. 67%
D. 85%
E. >99%
F. None of the above
C. 67%
4 yo boy with delayed walking, Gowers sign, CK 26,000 and muscle biopsy showing fatty replacement with fibrosis and myopathic features. Western blot was abnormal. A molecular study showed a frameshift mutation. The deletion was not detected in his mother but was detected in his 1-month old brother. Which of the following would most likely be the explanation of this phenomenon?
A. Incomplete penetrance
B. Variable expression
C. De novo mutations
D. Germline mosacisim
E. X inactivation
F. None of the above
D. Germline mosacisim
4 yo boy with delayed walking, Gowers sign, CK 26,000 and muscle biopsy showing fatty replacement with fibrosis and myopathic features. Western blot was abnormal. A molecular study showed a frameshift mutation. He was diagnosed with DMD. The same deletion was detected in his mother. The proband’s parents asked about the recurrent risk in future pregnancies. Which one of the following would be the most appropriate estimation of the recurrent risk in the family?
A. <1%
B. 5%
C. 25%
D. 36%
E. None of the above
B. 5%
20% (risk of maternal mosaicism) x 1/2 x 1/2
An 8-year old boy presented with difficulty walking and muscle weakness. He was from non-consanguineous parents and had one healthy brother and two health sisters. No other family members were affected. Pelvic and pectoral weakness along with a Gowers sign were present. Serum CK and aldolase were 50x normal. Molecular genetics study showed an out of frame deletion in the DMD gene. Which one of the following conditions would this patient most likely have?
A. BMD
B. DMD
C. DMD-associated dilated CM
D. Uncertain
E. None of the above
B. DMD
in frame deletion = BM
out of frame deletions = DMD
First exon and promoter = DCM
An 18 yo man with myopathy showed an in-frame deletion of exons 45-49 of DMD by multiplex ligation-dependent probe amplification (MLPA). There was no family history. MLPA showed an in-frame deletion. Which of the following conditions would this patient most likely have?
A. BMD
B. DMD
C. DMD-associated DCM
D. Uncertain
E. None of the above
A. BMD
An 8-year old boy presented with difficulty walking and muscle weakness. He was from non-consanguineous parents and had one healthy brother and two health sisters. No other family members were affected. Pelvic and pectoral weakness along with a Gowers sign were present. Serum CK and aldolase were 50x normal. EMG showed low amplitudes with no evidence of conduction delay. Molecular genetics study showed an out of frame deletion in the DMD gene. Which recommendations would be appropriate in the molecular genetics report?
A. Genetic counseling
B. Maternal testing
C. Paternal testing
D. Prenatal testing for future pregnancies
E. A and B
F. A and C
G. A, B and C
H. A, B and D
I. A, C and D
J. A, B, C and D
H. A, B and D
An 8-year old boy presented with difficulty walking and muscle weakness. He was from non-consanguineous parents and had one healthy brother and two health sisters. No other family members were affected. Pelvic and pectoral weakness along with a Gowers sign were present. Serum CK and aldolase were 50x normal. EMG showed low amplitudes with no evidence of conduction delay. Molecular genetics study showed an out of frame deletion in the DMD gene. Which mechanism would mostly likely contribute tot he pathogenesis of DMD in this patient?
A. Dominant negative
B. Gain of function
C. Loss of function
D. None of the above
C. Loss of function
