Microcephaly
Gene: CRNKL1
CRNKL1 (crooked neck pre-mRNA splicing factor 1)
EnsemblGeneIds (GRCh38): ENSG00000101343
EnsemblGeneIds (GRCh37): ENSG00000101343
OMIM: 610952, Gene2Phenotype
CRNKL1 is in 4 panels
EnsemblGeneIds (GRCh38): ENSG00000101343
EnsemblGeneIds (GRCh37): ENSG00000101343
OMIM: 610952, Gene2Phenotype
CRNKL1 is in 4 panels
1 review
Mark Cleghorn (Royal Melbourne Hospital)
Unpublished, presented at ESHG June 2024 - Louise Bicknell, University of Otago NZ
8 unrelated families via gene matcher with rare, de novo, missense variants in CRNKL1
severe microcephaly (all, -8 to -11 SD)
ID/epilepsy
pontocerebellar hypoplasia (6/8)
simplified gyration (8/8)
7 variants are missense at p.Arg267 residue
1 variant missense at p.Arg301
RNA-seq on patient fibroblasts - no alteration in gene expression
Zebrafish homolog of Arg267 and Arg301 - mimics observed phenotype (reduced brain development), increased in embryo apoptosis
RNQ seq on affected zebrafish embryos - transcriptome strongly disrupted
Splicing analysis in progress
CRKNL1 supports U6 structure in spliceosome
Sources: OtherCreated: 18 Jul 2024, 2:32 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
complex neurodevelopmental disorder MONDO:0100038
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
- Sources
-
- Expert Review Green
- Phenotypes
-
- complex neurodevelopmental disorder MONDO:0100038
- OMIM
- 610952
- Clinvar variants
- Variants in CRNKL1
- Penetrance
- None
- Panels with this gene
History Filter Activity
18 Jul 2024, Gel status: 3
Entity classified by Genomics England curator
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Gene: crnkl1 has been classified as Green List (High Evidence).
18 Jul 2024, Gel status: 3
Entity classified by Genomics England curator
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Gene: crnkl1 has been classified as Green List (High Evidence).
18 Jul 2024, Gel status: 0
Created, Added New Source, Set mode of inheritance, Set Phenotypes
Mark Cleghorn (Royal Melbourne Hospital)gene: CRNKL1 was added gene: CRNKL1 was added to Microcephaly. Sources: Other Mode of inheritance for gene: CRNKL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: CRNKL1 were set to complex neurodevelopmental disorder MONDO:0100038 Review for gene: CRNKL1 was set to GREEN