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Novel SPEG mutations in congenital myopathies: Genotype–phenotype correlations
Author(s) -
Qualls Anita E.,
Donkervoort Sandra,
Herkert Johanna C.,
D'gama Alissa M.,
BharuchaGoebel Diana,
Collins James,
Chao Katherine R.,
Foley A. Reghan,
Schoots Mirthe H.,
Jongbloed Jan D.H.,
Bönnemann Carsten G.,
Agrawal Pankaj B.
Publication year - 2019
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.26378
Subject(s) - phenotype , muscle biopsy , genotype , proximal muscle weakness , mutation , weakness , genetics , muscle weakness , chronic progressive external ophthalmoplegia , exome sequencing , compound heterozygosity , myopathy , biology , external ophthalmoplegia , pathology , medicine , gene , biopsy , mitochondrial myopathy , anatomy , mitochondrial dna
ABSTRACT Introduction : Centronuclear myopathies (CNMs) are a subtype of congenital myopathies (CMs) characterized by muscle weakness, predominant type 1 fibers, and increased central nuclei. SPEG (striated preferentially expressed protein kinase) mutations have recently been identified in 7 CM patients (6 with CNMs). We report 2 additional patients with SPEG mutations expanding the phenotype and evaluate genotype–phenotype correlations associated with SPEG mutations. Methods : Using whole exome/genome sequencing in CM families, we identified novel recessive SPEG mutations in 2 patients. Results : Patient 1, with severe muscle weakness requiring respiratory support, dilated cardiomyopathy, ophthalmoplegia, and findings of nonspecific CM on muscle biopsy carried a homozygous SPEG mutation (p.Val3062del). Patient 2, with milder muscle weakness, ophthalmoplegia, and CNM carried compound heterozygous mutations (p.Leu728Argfs*82) and (p.Val2997Glyfs*52). Conclusions : The 2 patients add insight into genotype–phenotype correlations of SPEG ‐associated CMs. Clinicians should consider evaluating a CM patient for SPEG mutations even in the absence of CNM features. Muscle Nerve 59 :357–362, 2019