Unknown

Dataset Information

0

Loss of function mutations in CCDC32 cause a congenital syndrome characterized by craniofacial, cardiac and neurodevelopmental anomalies.

ABSTRACT: Despite the wide use of genomics to investigate the molecular basis of rare congenital malformations, a significant fraction of patients remains bereft of diagnosis. As part of our continuous effort to recruit and perform genomic and functional studies on such cohorts, we investigated the genetic and mechanistic cause of disease in two independent consanguineous families affected by overlapping craniofacial, cardiac, laterality and neurodevelopmental anomalies. Using whole exome sequencing, we identified homozygous frameshift CCDC32 variants in three affected individuals. Functional analysis in a zebrafish model revealed that ccdc32 depletion recapitulates the human phenotypes. Because some of the patient phenotypes overlap defects common to ciliopathies, we asked if loss of CCDC32 might contribute to the dysfunction of this organelle. Consistent with this hypothesis, we show that ccdc32 is required for normal cilia formation in zebrafish embryos and mammalian cell culture, arguing that ciliary defects are at least partially involved in the pathomechanism of this disorder.

SUBMITTER: Harel T 

PROVIDER: S-EPMC7268788 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Loss of function mutations in CCDC32 cause a congenital syndrome characterized by craniofacial, cardiac and neurodevelopmental anomalies.

Harel Tamar T   Griffin John N JN   Arbogast Thomas T   Monroe Tanner O TO   Palombo Flavia F   Martinelli Marcella M   Seri Marco M   Pippucci Tommaso T   Elpeleg Orly O   Katsanis Nicholas N  

Human molecular genetics 20200601 9

Despite the wide use of genomics to investigate the molecular basis of rare congenital malformations, a significant fraction of patients remains bereft of diagnosis. As part of our continuous effort to recruit and perform genomic and functional studies on such cohorts, we investigated the genetic and mechanistic cause of disease in two independent consanguineous families affected by overlapping craniofacial, cardiac, laterality and neurodevelopmental anomalies. Using whole exome sequencing, we i  ...[more]

Similar Datasets

Transcriptomics INTS8 mutations cause severe neurodevelopmental syndrome
2017-05-17 | E-GEOD-76878 | biostudies-arrayexpress
Unknown Novel truncating mutations in CTNND1 cause a dominant craniofacial and cardiac syndrome.
| S-EPMC7372553 | biostudies-literature
Transcriptomics INTS8 mutations cause severe neurodevelopmental syndrome
2017-05-17 | GSE76878 | GEO
Unknown Mutations in TMEM260 Cause a Pediatric Neurodevelopmental, Cardiac, and Renal Syndrome.
| S-EPMC5384036 | biostudies-literature
Unknown De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies.
| S-EPMC4890146 | biostudies-literature
Unknown BRF1 mutations alter RNA polymerase III-dependent transcription and cause neurodevelopmental anomalies.
| S-EPMC4315290 | biostudies-literature
Transcriptomics Mutations in GEMIN5 cause a neurodevelopmental ataxia syndrome by a loss-of-1function mechanism
2021-03-11 | GSE168622 | GEO
Unknown Germline mutations in ABL1 cause an autosomal dominant syndrome characterized by congenital heart defects and skeletal malformations.
| S-EPMC5373987 | biostudies-literature
Unknown De Novo Mutations in EBF3 Cause a Neurodevelopmental Syndrome.
| S-EPMC5223060 | biostudies-literature
Unknown Loss of function mutations in GEMIN5 cause a neurodevelopmental disorder.
| S-EPMC8105379 | biostudies-literature