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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Kolanczyk, M; Krawitz, P; Hecht, J; Hupalowska, A; Miaczynska, M; Marschner, K; Schlack, C; Emmerich, D; Kobus, K; Kornak, U; Robinson, PN; Plecko, B; Grangl, G; Uhrig, S; Mundlos, S; Horn, D.
Missense variant in CCDC22 causes X-linked recessive intellectual disability with features of Ritscher-Schinzel/3C syndrome.
Eur J Hum Genet. 2015; 23(5):633-638 (- Case Report) [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Autor/innen der Med Uni Graz:
Grangl Gernot
Plecko Barbara
Uhrig Sabine

Dimensions Citations:

Plum Analytics:
Number of Figures: 4
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Ritscher-Schinzel syndrome (RSS)/3C (cranio-cerebro-cardiac) syndrome (OMIM#220210) is a rare and clinically heterogeneous developmental disorder characterized by intellectual disability, cerebellar brain malformations, congenital heart defects, and craniofacial abnormalities. A recent study of a Canadian cohort identified homozygous sequence variants in the KIAA0196 gene, which encodes the WASH complex subunit strumpellin, as a cause for a form of RSS/3C syndrome. We have searched for genetic causes of a phenotype similar to RSS/3C syndrome in an Austrian family with two affected sons. To search for disease-causing variants, whole-exome sequencing (WES) was performed on samples from two affected male children and their parents. Before WES, CGH array comparative genomic hybridization was applied. Validation of WES and segregation studies was done using routine Sanger sequencing. Exome sequencing detected a missense variant (c.1670A>G; p.(Tyr557Cys)) in exon 15 of the CCDC22 gene, which maps to chromosome Xp11.23. Western blots of immortalized lymphoblastoid cell lines (LCLs) from the affected individual showed decreased expression of CCDC22 and an increased expression of WASH1 but a normal expression of strumpellin and FAM21 in the patients cells. We identified a variant in CCDC22 gene as the cause of an X-linked phenotype similar to RSS/3C syndrome in the family described here. A hypomorphic variant in CCDC22 was previously reported in association with a familial case of syndromic X-linked intellectual disability, which shows phenotypic overlap with RSS/3C syndrome. Thus, different inactivating variants affecting CCDC22 are associated with a phenotype similar to RSS/3C syndrome.
Find related publications in this database (using NLM MeSH Indexing)
Abnormalities, Multiple - diagnosis
Abnormalities, Multiple - genetics
Adolescent -
Amino Acid Sequence -
Cell Line -
Child -
Comparative Genomic Hybridization -
Craniofacial Abnormalities - diagnosis
Craniofacial Abnormalities - genetics
Dandy-Walker Syndrome - diagnosis
Dandy-Walker Syndrome - genetics
Exome -
Gene Expression -
Genes, X-Linked -
Genetic Association Studies -
Heart Septal Defects, Atrial - diagnosis
Heart Septal Defects, Atrial - genetics
High-Throughput Nucleotide Sequencing -
Humans -
Intellectual Disability - diagnosis
Intellectual Disability - genetics
Male -
Molecular Sequence Data -
Mutation, Missense -
Pedigree -
Phenotype -
Proteins - chemistry
Proteins - genetics
Sequence Alignment -

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