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<jats:title>Abstract</jats:title><jats:p><jats:italic>ATP2B1</jats:italic> 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 <jats:italic>ATP2B1</jats:italic> 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 <jats:italic>ATP2B1</jats:italic> variants: a maternally inherited splice-site (c.3060+2 T > G) and paternally inherited missense c.2938 G > T; p.(Val980Leu). Reverse-transcription-PCR on the proband’s fibroblast-derived mRNA showed aberrantly spliced <jats:italic>ATP2B1</jats:italic> transcripts targeted for nonsense-mediated decay. All correctly-spliced <jats:italic>ATP2B1</jats:italic> mRNA encoding p.(Val980Leu) functionally causes decreased cellular Ca<jats:sup>2+</jats:sup> extrusion. Immunoblotting showed reduced fibroblast ATP2B1. We conclude that biallelic <jats:italic>ATP2B1</jats:italic> variants are the likely cause of the proband’s phenotype, strengthening the association of <jats:italic>ATP2B1</jats:italic> as a neurodevelopmental gene and expanding the phenotypic characterization of a biallelic loss-of-function genotype.</jats:p>
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Hinweis
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DeepGreen-ID: 038b5788264642f0becf2f272ad88a85 ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
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