Screening of a clinically and biochemically diagnosed SOD patient using exome sequencing : a case report with a mutations variations analysis approach

Abstract EN

Background: Sulfite oxidase deficiency (SOD) is a rare neurometabolic inherited disorder causing severe delay in developmental stages and premature death.

The disease follows an autosomal recessive pattern of inheritance and causes deficiency in the activity of sulfite oxidase, an enzyme that normally catalyzes conversion of sulfite to sulfate.

Aim of the study: SOD is an underdiagnosed disorder and its diagnosis can be difficult in young infants as early clinical features and neuroimaging changes may imitate some common diseases.

Since the prognosis of the disease is poor, using exome sequencing as a powerful and efficient strategy for identifying the genes underlying rare mendelian disorders can provide important knowledge about early diagnosis, disease mechanisms, biological pathways, and potential therapeutic targets.

Patients and methods: In this study, a case who was a newborn infant boy with suspected SOD and his healthy parents were recruited for exome sequencing.

The first laboratory reports of the patient were positive urine sulfite, elevated urinary thiosulfate, and high levels of plasma lactate and pyruvate.

The patient also presented some symptoms such as intractable seizures, abnormal tone, feeding difficulties, profound mental retardation, abnormal respiratory drive, aspiration pneumonia, microcephaly, and dislocated ocular lenses.

The genomic DNA of the patient and his parents was extracted from peripheral blood lymphocytes as targets for exome sequencing, performed by Axeq Technologies (Amsterdam, the Netherlands).

Results: The results showed no single predominate mutation in the SUOX gene as one of the candidate genes involved in the catabolism of sulfur-containing amino acids.

The same results obtained in the molybdenum cofactor biosynthetic genes (MOCS1, MOCS2, and GEPH genes).

Instead, the results revealed that causal variations are present in genes underlying in different biochemical pathways among which the sulfur metabolism, signaling and signal transduction, and transcription pathways are of higher importance.

Conclusion: In this study, several classes of genes were introduced as candidate genes involved in SOD.

However, further studies are necessary to examine the reported genes in more details on how these genes may relate to each other and contribute to the pathology of SOD disease.