RNASET2-deficient leukoencephalopathy mimicking congenital CMV infection and Aicardi-Goutieres syndrome: a case report with a novel pathogenic variant

Abstract

Background Ribonucleases (RNases) are crucial for degradation of ribosomal RNA (rRNA). RNASET2 as a subtype of RNASEs is a 256 amino acid protein, encoded by RNASET2 gene located on chromosome six. Defective RNASET2 leads to RNASET2 - deficient leukoencephalopathy, a rare autosomal recessive neurogenetic disorder with psychomotor delay as its main clinical symptom. The clinical findings can be similar to congenital cytomegalovirus (CMV) infection and Aicardi-Goutieres syndrome (AGS). Methods Herein, we presented a patient with motor delay, neurological regression, infrequent seizures and microcephaly at 5 months of age. Brain imaging showed white matter involvement, calcification and anterior temporal cysts. Basic metabolic tests, serum and urine CMV polymerase chain reaction (PCR) were requested. According to clinical and imaging findings, screening of RNASET2 and RMND1 genes were performed. The clinical data and magnetic resonance imaging (MRI) findings of previous reported individuals with RNASET2-deficient leukodystrophy were also reviewed and compared to the findings of our patient. Results Brain MRI findings were suggestive of RNASET2 - deficient leukoencephalopathy, AGS and CMV infection. Basic metabolic tests were normal and CMV PCR was negative. Molecular study revealed a novel homozygous variant of c.233C > A; p.Ser78Ter in exon 4 of RNASET2 gene compatible with the diagnosis of RNASET2 - deficient leukoencephalopathy. Conclusions RNASET2-deficiency is a possible diagnosis in an infant presented with a static leukoencephalopathy and white matter involvement without megalencephaly. Due to overlapping clinical and radiologic features of RNASET2-deficient leukoencephalopathy, AGS and congenital CMV infections, molecular study as an important and helpful diagnostic tool should be considered to avoid misdiagnosis.

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“…Mutations of complex I subunits result in numerous clinical presentations including leukodystrophy, optic neuropathy, and encephalopathy (reviewed in [ 41 , 42 ]). Interestingly, leukodystrophy and congenital CMV are difficult to distinguish [ 43 ].…”

The Potential Role of the T2 Ribonucleases in TME-Based Cancer Therapy

“…A case report performed using brain imaging analysis on a 5-month-old patient with motor delay, neurological regression, infrequent seizures, and microcephaly revealed the presence of white matter abnormalities, calcification, and cysts in the anterior temporal region [ 84 ]. To investigate the underlying cause, the authors performed a screening for mutations in the RNASET2 and RMND1 genes together with a comprehensive review of previously reported cases of individuals with RNASET2-deficient leukodystrophy, comparing their clinical data and magnetic resonance imaging (MRI) with the observation reported in the case report.…”

“…To investigate the underlying cause, the authors performed a screening for mutations in the RNASET2 and RMND1 genes together with a comprehensive review of previously reported cases of individuals with RNASET2-deficient leukodystrophy, comparing their clinical data and magnetic resonance imaging (MRI) with the observation reported in the case report. Using this analysis, the authors identified a novel homozygous variant of c.233C > A; p.Ser78Ter in exon 4 of the RNASET2 gene compatible with the diagnosis of RNASET2-deficient leukoencephalopathy [ 84 ].…”