PEHO syndrome caused by compound heterozygote variants in ZNHIT3 gene.

TitlePEHO syndrome caused by compound heterozygote variants in ZNHIT3 gene.
Publication TypeJournal Article
Year of Publication2020
AuthorsÕunap, K, Muru, K, Õiglane-Shlik, E, Ilves, P, Pajusalu, S, Kuus, I, Wojcik, MH, Reimand, T
JournalEur J Med Genet
Date Published2020 Feb

PEHO syndrome is characterized by Progressive Encephalopathy with Edema, Hypsarrhythmia, and Optic atrophy, which was first described in Finnish patients. A homozygous missense substitution p.Ser31Leu in ZNHIT3 was recently identified as the primary cause of PEHO syndrome in Finland. Variants in ZNHIT3 have not been identified in patients with PEHO or PEHO-like syndrome in other populations. It has therefore been suggested that PEHO syndrome caused by ZNHIT3 variants does not occur outside of the Finnish population. We describe the first patient outside Finland who carries compound heterozygous variants in ZNHIT3 gene causing PEHO syndrome. Trio genome sequencing was carried out and the identified variants were confirmed by Sanger sequencing. The patient filled all diagnostic clinical criteria of PEHO syndrome. We identified biallelic missense variants in ZNHIT3 gene: the c.92C > T p.(Ser31Leu) variant (NM_004773.3), which is described previously as causing PEHO syndrome and the second novel variant c.41G > T p.(Cys14Phe). There are only eight heterozygous carriers of c.41G > T variant in the gnomAD database and it is predicted damaging by multiple in silico algorithms. The ZNHIT3-associated PEHO syndrome exists outside of the Finnish population.

Alternate JournalEur J Med Genet
PubMed ID31048081
PubMed Central IDPMC6819237
Grant ListT32 GM007748 / GM / NIGMS NIH HHS / United States
UM1 HG008900 / HG / NHGRI NIH HHS / United States