Format

Send to

Choose Destination
Genome Med. 2016 Jan 6;8(1):3. doi: 10.1186/s13073-015-0253-0.

POGZ truncating alleles cause syndromic intellectual disability.

Author information

1
Department of Molecular and Human Genetics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, 77030, USA.
2
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA.
3
Ambry Genetics, Aliso Viejo, CA, 92656, USA.
4
Children's Hospitals and Clinics of Minnesota, Minneapolis, MN, 55102, USA.
5
Arnold Palmer Medical Center, Division of Genetics, Orlando, FL, 32806, USA.
6
University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
7
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, 37212, USA.
8
Exome Laboratory, Baylor Miraca Genetics Laboratory, Houston, TX, 77030, USA.
9
Texas Children's Hospital, Houston, TX, 77030, USA.
10
Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.
11
University of Texas Health Science Center, Houston, TX, USA.
12
Department of Molecular and Human Genetics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, 77030, USA. vrsutton@texaschildrens.org.

Abstract

BACKGROUND:

Large-scale cohort-based whole exome sequencing of individuals with neurodevelopmental disorders (NDDs) has identified numerous novel candidate disease genes; however, detailed phenotypic information is often lacking in such studies. De novo mutations in pogo transposable element with zinc finger domain (POGZ) have been identified in six independent and diverse cohorts of individuals with NDDs ranging from autism spectrum disorder to developmental delay.

METHODS:

Whole exome sequencing was performed on five unrelated individuals. Sanger sequencing was used to validate variants and segregate mutations with the phenotype in available family members.

RESULTS:

We identified heterozygous truncating mutations in POGZ in five unrelated individuals, which were confirmed to be de novo or not present in available parental samples. Careful review of the phenotypes revealed shared features that included developmental delay, intellectual disability, hypotonia, behavioral abnormalities, and similar facial characteristics. Variable features included short stature, microcephaly, strabismus and hearing loss.

CONCLUSIONS:

While POGZ has been associated with neurodevelopmental disorders in large cohort studies, our data suggest that loss of function variants in POGZ lead to an identifiable syndrome of NDD with specific phenotypic traits. This study exemplifies the era of human reverse clinical genomics ushered in by large disease-directed cohort studies; first defining a new syndrome molecularly and, only subsequently, phenotypically.

PMID:
26739615
PMCID:
PMC4702300
DOI:
10.1186/s13073-015-0253-0
[Indexed for MEDLINE]
Free PMC Article

Publication type, MeSH terms, Substances, Grant support

Publication type

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center