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

Mamiko Yamada, Hisato Suzuki, Hiroyuki Adachi, Atsuko Noguchi, Fuyuki Miya, Tsutomu Takahashi, Kenjiro Kosaki

研究成果: Article査読

抄録

Background: 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. Case presentation: 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. Conclusion: 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.

本文言語English
論文番号20
ジャーナルBMC Neurology
22
1
DOI
出版ステータスPublished - 2022 12月

ASJC Scopus subject areas

  • 臨床神経学

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