Abstract | OBJECTIVE: METHODS: We performed molecular genetic, histochemical, immunoblot, and ultrastructural studies, investigated neuromuscular transmission in vitro in a patient with isolated PREPL deficiency, and evaluated the effect of pyridostigmine in this patient and in 3 patients with the HCS. RESULTS: HCS is caused by recessive deletions involving the SLC3A1 and PREPL genes. The major clinical features of HCS are type A cystinuria, growth hormone deficiency, muscle weakness, ptosis, and feeding problems. The proband with isolated PREPL deficiency had myasthenic symptoms since birth and a positive edrophonium test but no cystinuria. She and 1 of 3 patients with HCS responded transiently to pyridostigmine during infancy. The proband harbors a paternally inherited nonsense mutation in PREPL and a maternally inherited deletion involving both PREPL and SLC3A1; therefore, the PREPL deficiency determines the phenotype. We detected no PREPL expression in the patient's muscle and endplates. Electrophysiology studies revealed decreased quantal content of the endplate potential and reduced amplitude of the miniature endplate potential without endplate acetylcholine receptor deficiency or altered endplate geometry. CONCLUSION:
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Authors | Luc Régal, Xin-Ming Shen, Duygu Selcen, Chantal Verhille, Sandra Meulemans, John W M Creemers, Andrew G Engel |
Journal | Neurology
(Neurology)
Vol. 82
Issue 14
Pg. 1254-60
(Apr 08 2014)
ISSN: 1526-632X [Electronic] United States |
PMID | 24610330
(Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Serine Endopeptidases
- PREPL protein, human
- Prolyl Oligopeptidases
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Topics |
- Chromosomes, Human, Pair 2
(genetics)
- Cystinuria
(complications, genetics)
- Female
- Gene Deletion
- Humans
- Infant
- Muscle Weakness
(genetics)
- Muscle, Skeletal
(metabolism, ultrastructure)
- Myasthenic Syndromes, Congenital
(diagnosis, etiology, genetics, physiopathology)
- Phenotype
- Prolyl Oligopeptidases
- Serine Endopeptidases
(deficiency, metabolism)
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