biostudies-literatureMagyar CLTexas Children's HospitalBurroughs Wellcome FundNHGRI NIH HHSBaylor College of MedicineChild Neurology FoundationRobert and Janice McNair FoundationNational Institutes of HealthNIH HHS1868-1874https://www.ebi.ac.uk/biostudies/studies/S-EPMC11149102biostudies-literatureUnknown188(6)Prune exopolyphosphatase-1 (PRUNE1) encodes a member of the aspartic acid-histidine-histidine (DHH) phosphodiesterase superfamily that regulates cell migration and proliferation during brain development. In 2015, biallelic PRUNE1 loss-of-function variants were identified to cause the neurodevelopmental disorder with microcephaly, hypotonia, and variable brain abnormalities (NMIHBA, OMIM#617481). NMIHBA is characterized by the namesake features and structural brain anomalies including thinning of the corpus callosum, cerebral and cerebellar atrophy, and delayed myelination. To date, 47 individuals have been reported in the literature, but the phenotypic spectrum of PRUNE1-related disorders and their causative variants remains to be characterized fully. Here, we report a novel homozygous PRUAmerican journal of medical genetics. Part APRUNE1 c.933G>A synonymous variant induces exon 7 skipping, disrupts the DHHA2 domain, and leads to an atypical NMIHBA syndrome presentation: Case report and review of the literature.PMC11149102DP5OD026428DP5 OD026428U01 HG007942U01HG007942U01 HG007709U01HG007709Gibson JBUndiagnosed Diseases NetworkRosenfeld JATran AABurrage LCLin YMurdock DRLalani SRBacino CALee BHChao HTAstudillo MFMagyar CLLewis RADai HfalsePRUNE1 c.933G>A synonymous variant induces exon 7 skipping, disrupts the DHHA2 domain, and leads to an atypical NMIHBA syndrome presentation: Case report and review of the literature.Prune exopolyphosphatase-1 (PRUNE1) encodes a member of the aspartic acid-histidine-histidine (DHH) phosphodiesterase superfamily that regulates cell migration and proliferation during brain development. In 2015, biallelic PRUNE1 loss-of-function variants were identified to cause the neurodevelopmental disorder with microcephaly, hypotonia, and variable brain abnormalities (NMIHBA, OMIM#617481). NMIHBA is characterized by the namesake features and structural brain anomalies including thinning of the corpus callosum, cerebral and cerebellar atrophy, and delayed myelination. To date, 47 individuals have been reported in the literature, but the phenotypic spectrum of PRUNE1-related disorders and their causative variants remains to be characterized fully. Here, we report a novel homozygous PRU2022-01-01T00:00:00Z2022 Jun2026-04-14T03:18:17.161Z2026-04-14T03:07:03.801ZS-EPMC111491023519493810.1002/ajmg.a.62704