@article {561, title = {Novel SPEG mutations in congenital myopathies: Genotype-phenotype correlations.}, journal = {Muscle Nerve}, volume = {59}, year = {2019}, month = {2019 03}, pages = {357-362}, 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.

}, keywords = {Biopsy, Child, Child, Preschool, Consanguinity, Exome, Female, Genetic Association Studies, Humans, Infant, Male, Muscle Proteins, Muscle Weakness, Muscle, Skeletal, Mutation, Myopathies, Structural, Congenital, Protein-Serine-Threonine Kinases, Sequence Analysis}, issn = {1097-4598}, doi = {10.1002/mus.26378}, author = {Qualls, Anita E and Donkervoort, Sandra and Herkert, Johanna C and D{\textquoteright}Gama, Alissa M and Bharucha-Goebel, Diana and Collins, James and Chao, Katherine R and Foley, A Reghan and Schoots, Mirthe H and Jongbloed, Jan D H and B{\"o}nnemann, Carsten G and Agrawal, Pankaj B} } @article {145, title = {Generation of sequence-based data for pedigree-segregating Mendelian or Complex traits.}, journal = {Bioinformatics}, volume = {31}, year = {2015}, month = {2015 Nov 15}, pages = {3706-8}, abstract = {

MOTIVATION: There is great interest in analyzing next generation sequence data that has been generated for pedigrees. However, unlike for population-based data there are only a limited number of rare variant methods to analyze pedigree data. One limitation is the ability to evaluate type I and II errors for family-based methods, due to lack of software that can simulate realistic sequence data for pedigrees.

SUMMARY: We developed RarePedSim (Rare-variant Pedigree-based Simulator), a program to simulate region/gene-level genotype and phenotype data for complex and Mendelian traits for any given pedigree structure. Using a genetic model, sequence variant data can be generated either conditionally or unconditionally on pedigree members{\textquoteright} qualitative or quantitative phenotypes. Additionally, qualitative or quantitative traits can be generated conditional on variant data. Sequence data can either be simulated using realistic population demographic models or obtained from sequence-based studies. Variant sites can be annotated with positions, allele frequencies and functionality. For rare variants, RarePedSim is the only program that can efficiently generate both genotypes and phenotypes, regardless of pedigree structure. Data generated by RarePedSim are in standard Linkage file (.ped) and Variant Call (.vcf) formats, ready to be used for a variety of purposes, including evaluation of type I error and power, for association methods including mixed models and linkage analysis methods.

AVAILABILITY AND IMPLEMENTATION: bioinformatics.org/simped/rare

CONTACT: sleal@bcm.edu.

}, keywords = {Base Sequence, Chromosome Segregation, Humans, Pedigree, Quantitative Trait, Heritable, Sequence Analysis, Software}, issn = {1367-4811}, doi = {10.1093/bioinformatics/btv412}, author = {Li, Biao and Wang, Gao T and Leal, Suzanne M} }