RGD Reference Report - Genomic analysis of primordial dwarfism reveals novel disease genes. - Rat Genome Database

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Genomic analysis of primordial dwarfism reveals novel disease genes.

Authors: Shaheen, R  Faqeih, E  Ansari, S  Abdel-Salam, G  Al-Hassnan, ZN  Al-Shidi, T  Alomar, R  Sogaty, S  Alkuraya, FS 
Citation: Shaheen R, etal., Genome Res. 2014 Feb;24(2):291-9. doi: 10.1101/gr.160572.113. Epub 2014 Jan 3.
RGD ID: 8694132
Pubmed: (View Article at PubMed) PMID:24389050
DOI: Full-text: DOI:10.1101/gr.160572.113

Primordial dwarfism (PD) is a disease in which severely impaired fetal growth persists throughout postnatal development and results in stunted adult size. The condition is highly heterogeneous clinically, but the use of certain phenotypic aspects such as head circumference and facial appearance has proven helpful in defining clinical subgroups. In this study, we present the results of clinical and genomic characterization of 16 new patients in whom a broad definition of PD was used (e.g., 3M syndrome was included). We report a novel PD syndrome with distinct facies in two unrelated patients, each with a different homozygous truncating mutation in CRIPT. Our analysis also reveals, in addition to mutations in known PD disease genes, the first instance of biallelic truncating BRCA2 mutation causing PD with normal bone marrow analysis. In addition, we have identified a novel locus for Seckel syndrome based on a consanguineous multiplex family and identified a homozygous truncating mutation in DNA2 as the likely cause. An additional novel PD disease candidate gene XRCC4 was identified by autozygome/exome analysis, and the knockout mouse phenotype is highly compatible with PD. Thus, we add a number of novel genes to the growing list of PD-linked genes, including one which we show to be linked to a novel PD syndrome with a distinct facial appearance. PD is extremely heterogeneous genetically and clinically, and genomic tools are often required to reach a molecular diagnosis.


Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Dna2  (DNA replication helicase/nuclease 2)

Genes (Mus musculus)
Dna2  (DNA replication helicase/nuclease 2)

Genes (Homo sapiens)
DNA2  (DNA replication helicase/nuclease 2)

Additional Information