Diagnosis of SLC25A46-related pontocerebellar hypoplasia in two siblings with fulminant neonatal course: role of postmortem CT and whole genomic analysis: a case report

Pontocerebellar hypoplasia (PCH) is increasingly known as a degenerative disease rather than simple "hypoplasia". At least 21 disease-causing genes have been identified for PCH so far. Because PCH is very heterogenous, prognostic prediction based solely on clinical or radiologic findings i...

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Bibliographic Details
Published in:BMC neurology 2022-01, Vol.22 (1), p.20-20, Article 20
Main Authors: Yamada, Mamiko, Suzuki, Hisato, Adachi, Hiroyuki, Noguchi, Atsuko, Miya, Fuyuki, Takahashi, Tsutomu, Kosaki, Kenjiro
Format: Article
Language:English
Subjects:
Abnormalities
Ascites
Atrophy
Brain
Brothers and sisters
Case Report
Case studies
Cerebellar Diseases - diagnosis
Cerebellar Diseases - genetics
Computed tomography
Fatal Outcome
Gene deletion
Genes
Genetic aspects
Genetic counseling
Genetic screening
Genetic variation
Genomes
Genomic analysis
Genomics
Health aspects
Humans
Hypoplasia
Infant, Newborn
Mitochondria
Mitochondrial Proteins - genetics
Mutation
Neonates
Neuroimaging
Parents & parenting
Patients
Pediatric research
Phosphate Transport Proteins - genetics
Pontocerebellar hypoplasia
Respiration
Siblings
SLC25A46
Tomography, X-Ray Computed
Whole genome sequencing
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Summary:Pontocerebellar hypoplasia (PCH) is increasingly known as a degenerative disease rather than simple "hypoplasia". At least 21 disease-causing genes have been identified for PCH so far. Because PCH is very heterogenous, prognostic prediction based solely on clinical or radiologic findings is not feasible. Here, we report two siblings who had a fulminant neonatal course. The documentation of pontocerebellar hypoplasia by postmortem brain CT imaging in one of the siblings and a subsequent complex and comprehensive whole genome analysis established that both siblings had bi-allelic compound heterozygous variants (a splicing variant and a deletion) in the SLC25A46 gene which encodes a solute carrier protein essential for mitochondrial function. Long-read whole genome sequencing was required to confirm the presence of the deletion. The fulminant courses suggest that SLC25A46-related PCH is an acutely progressive degenerative condition starting in utero, rather than a simple static hypoplasia. The genomic analysis was instrumental and essential to solving the enigma of the unexplained neonatal deaths of these two siblings and to provide accurate genetic counseling.
ISSN:1471-2377
1471-2377
DOI:10.1186/s12883-021-02540-x