Molecular diagnosis of asparagine synthetase (ASNS) deficiency in two Indian families and literature review of 29 ASNS deficient cases

• Published in: Gene Vol. 704; pp. 97 - 102
• Main Authors: Radha Rama Devi, Akella, Naushad, Shaik Mohammad
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2019
• Subjects: ASNS gene; Asparagine synthetase deficiency; In silico characterization; Microcephaly; SD; ASNS gene; ExAC; EEG; ASNS; TMS; Microcephaly; In silico characterization; Asparagine synthetase deficiency
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2019.04.024

In the current study, we report three cases of Asparagine Synthetase (ASNS) Deficiency from two consanguineous families. Family 1 had two early neonatal deaths due to a novel mutation in the ASNS gene c.788C > T (p.S263F) and both the children presented with microcephaly and one of them had severe intracranial haemorrhage. The proband from the second family was homozygous for c.146G > A (p.R49Q) and manifested myoclonic seizures, developmental delay, coarse hair and diffuse cortical atrophy. Molecular docking studies of both the mutations revealed alteration in the ligand binding site. Till date, 26 mutations were reported in ASNS gene in 29 affected children indicating high degree of genetic heterogeneity and high mortality. Although asparagine depletion is not of diagnostic utility, multiple linear regression model suggested that asparagine levels vary to the extent of 20.6% based on glutamine and aspartate levels and ASNS deficiency results in depletion of asparagine synthesis. ASNS deficiency should be suspected in any neonate with microcephaly and epileptic encephalopathy. •Three cases of ASNS Deficiency were reported from two consanguineous Indian families•Family 1 with ASNS c.788 C>T (p.S263F) mutation had two early neonatal deaths•Manifested with microcephaly and severe intracranial haemorrhage•Family 2 with ASNS c.146G>A (R49Q) mutation showed diffuse cortical atrophy•Till date, 26 ASNS mutations were reported in 29 affected children