biostudies-literatureYap PDepartment of Health | National Health and Medical Research Council (NHMRC)125-129https://www.ebi.ac.uk/biostudies/studies/S-EPMC10772071biostudies-literatureUnknown32(1)ATP2B1 encodes plasma membrane calcium-transporting-ATPase1 and plays an essential role in maintaining intracellular calcium homeostasis that regulates diverse signaling pathways. Heterozygous de novo missense and truncating ATP2B1 variants are associated with a neurodevelopmental phenotype of variable expressivity. We describe a proband with distinctive craniofacial gestalt, Pierre-Robin sequence, neurodevelopmental and growth deficit, periventricular heterotopia, brachymesophalangy, cutaneous syndactyly, and persistent hypocalcemia from primary hypoparathyroidism. Proband-parent trio exome sequencing identified compound heterozygous ATP2B1 variants: a maternally inherited splice-site (c.3060+2 T > G) and paternally inherited missense c.2938 G > T; p.(Val980Leu). Reverse-transcription-PCREuropean journal of human genetics : EJHGBiallelic ATP2B1 variants as a likely cause of a novel neurodevelopmental malformation syndrome with primary hypoparathyroidism.PMC10772071APP1136197Riley LGAlburaiky SRahimi MJLe Quesne Stabej PCurran BOppermann HPrint CCooper STBohlander SKKakadia PMHayes IYap PfalseBiallelic ATP2B1 variants as a likely cause of a novel neurodevelopmental malformation syndrome with primary hypoparathyroidism.ATP2B1 encodes plasma membrane calcium-transporting-ATPase1 and plays an essential role in maintaining intracellular calcium homeostasis that regulates diverse signaling pathways. Heterozygous de novo missense and truncating ATP2B1 variants are associated with a neurodevelopmental phenotype of variable expressivity. We describe a proband with distinctive craniofacial gestalt, Pierre-Robin sequence, neurodevelopmental and growth deficit, periventricular heterotopia, brachymesophalangy, cutaneous syndactyly, and persistent hypocalcemia from primary hypoparathyroidism. Proband-parent trio exome sequencing identified compound heterozygous ATP2B1 variants: a maternally inherited splice-site (c.3060+2 T > G) and paternally inherited missense c.2938 G > T; p.(Val980Leu). Reverse-transcription-PCR2024-01-01T00:00:00Z2024 Jan2026-06-12T05:51:39.986Z2025-04-03T21:31:04.263ZS-EPMC107720713792671310.1038/s41431-023-01484-9