Τίτλος:
New Compound Heterozygous Splice Site Mutations of the Skeletal Muscle Ryanodine Receptor (RYR1) Gene Manifest Fetal Akinesia: A Linkage with Congenital Myopathies
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Mutations in the skeletal muscle ryanodine receptor (RYR1) gene have been linked to malignant hyperthermia susceptibility, central core disease, and minicore myopathy with external ophthalmoplegia. RYR1 is an intracellular calcium release channel and plays a crucial role in the sarcoplasmic reticulum and transverse tubule connection. Here, we report 2 fetuses from the same parents with compound heterozygous mutations in the RYR1 gene (c.10347+1G>A and c.10456-2 >G) who presented with fetal akinesia and polyhydramnios at 27 and 19 weeks of gestation with intrauterine growth restriction in the third pregnancy. The prospective parents of the fetuses were heterozygous carriers for c.10456-2 >G (mother) and c.10347+1G>A (father). Both mutations affect splice sites resulting in dysfunctional protein forms probably missing crucial domains of the C-terminus. Our findings reveal a new RYR1 splice site mutation (c.10456-2 >G) that may be associated with the clinical features of myopathies, expanding the RYR1 spectrum related to these pathologies. © 2020 S. Karger AG, Basel.
Συγγραφείς:
Zecevic, N.
Arsenijevic, V.
Manolakos, E.
Papoulidis, I.
Theocharis, G.
Sartsidis, A.
Tsagas, T.
Tziotis, I.
Dagklis, T.
Kalogeros, G.
Tsakiridis, I.
Filipovic Stankovic, M.
Eleftheriades, M.
Περιοδικό:
Molecular Syndromology
Λέξεις-κλειδιά:
ryanodine receptor 1, akinesia; Article; carboxy terminal sequence; case report; chorion villus sampling; clinical article; clinical feature; copy number variation; disease association; DNA isolation; female; fetus; fetus echography; fetus movement; gene mutation; gene sequence; gene targeting; genetic association; genetic counseling; genetic linkage; gestational age; Greece; heterozygote; high throughput sequencing; human; hydramnios; intrauterine growth retardation; karyotyping; male; medical history; microarray analysis; myopathy; priority journal
