TASP1 mutation in a female with craniofacial anomalies, anterior segment dysgenesis, congenital immunodeficiency and macrocytic anemia.

Abstract

BACKGROUND:

Threonine Aspartase 1 (Taspase 1) is a highly conserved site-specific protease whose substrates are broad-acting nuclear transcription factors that govern diverse biological programs, such as organogenesis, oncogenesis, and tumor progression. To date, no single base pair mutations in Taspase 1 have been implicated in human disease.

METHODS:

A female infant with a new pattern of diagnostic abnormalities was identified, including severe craniofacial anomalies, anterior and posterior segment dysgenesis, immunodeficiency, and macrocytic anemia. Trio-based whole exome sequencing was performed to identify disease-causing variants.

RESULTS:

Whole exome sequencing revealed a normal female karyotype (46,XX) without increased regions of homozygosity. The proband was heterozygous for a de novo missense variant, c.1027G>A predicting p.(Val343Met), in the TASP1 gene (NM_017714.2). This variant has not been observed in population databases and is predicted to be deleterious.

CONCLUSION:

One human patient has been reported previously with a large TASP1 deletion and substantial evidence exists regarding the role of several known Taspase 1 substrates in human craniofacial and hematopoietic disorders. Moreover, Taspase 1 deficiency in mice results in craniofacial, ophthalmological and structural brain defects. Taken together, there exists substantial evidence to conclude that the TASP1 variant, p.(Val343Met), is pathogenic in this patient.

• Authors: Daniel M Balkin, Menitha Poranki, Craig M Forester, Morna J Dorsey, Anne Slavotinek, Jason H Pomerantz
• Journal: Molecular genetics & genomic medicine (Mol Genet Genomic Med) Vol. 7 Issue 9 Pg. e818 (09 2019) ISSN: 2324-9269 [Electronic] United States
• PMID: 31350873 (Publication Type: Case Reports, Journal Article)
• Copyright: © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Chemical References

• Biomarkers
• Endopeptidases
• taspase1, human

Topics

• Alleles
• Anemia, Macrocytic (diagnosis, genetics)
• Biomarkers
• Craniofacial Abnormalities (diagnosis, genetics)
• Endopeptidases (chemistry, genetics)
• Eye Abnormalities (diagnosis, genetics)
• Female
• Genetic Association Studies
• Genetic Predisposition to Disease
• Genotype
• Humans
• Imaging, Three-Dimensional
• Infant
• Infant, Newborn
• Magnetic Resonance Imaging
• Models, Biological
• Models, Molecular
• Mutation
• Mutation, Missense
• Phenotype
• Primary Immunodeficiency Diseases (diagnosis, genetics)
• Structure-Activity Relationship
• Exome Sequencing