Generation of an iPSC line (CRICKi001-A) from an individual with a germline SMARCA4 missense mutation and autism spectrum disorder

Abstract

Germline missense mutations in the BAF swi/snf chromatin remodeling subunit SMARCA4 are associated with neurodevelopmental disorders, including Coffin Siris Syndrome (CSS). Here, we generated an induced pluripotent stem cell line from a male patient with atypical CSS features and a de n ovo heterozygous missense mutation in the SMARCA4 gene (c.3607C>T, p.(Arg1203Cys)). Hair root derived keratinocytes were reprogrammed using non-integrative Sendai virus vector delivery of pluripotency factors. iPSCs generated display normal morphology and molecular karyotype, express pluripotency markers and are able to differentiate into the three germ layers.

BCL11A intellectual developmental disorder: defining the clinical spectrum and genotype-phenotype correlations

“…More recently, expanding phenotypes (e.g. SMARCA2, SMARCA4) 46,47 and novel BAF swi/snf genes involved in syndromic and non-syndromic IDD (e.g. ACTL6A, ACTL6B, SMARCC1) [48][49][50][51] without classical CSS and NCBRS physical features have broadened the spectrum of conditions considerably.…”

Generation of an MTM1-mutant iPSC line (CRICKi008-A) from an individual with X-linked myotubular myopathy (XLMTM)

“…For direct differentiation, we used the STEMdiff™ Trilineage Differentiation Kit (STEMCELL Technologies) as per manufacturer's instructions. We evaluated the differentiation potential of the CRICKi008-A line by immunostaining for lineage-specific markers on Day 5 (Mesoderm and Endoderm) and Day 7 (Ectoderm) as previously described (Devito et al, 2021). Differentiated cells were washed twice in DPBS (Ca 2 Mg 2 ) (Thermo Fisher Scientific) before fixation with 3.7% paraformaldehyde (Sigma-Aldrich) for 20 min at room temperature.…”