title: Three Novel Spectrin Variants in Jaundiced Neonates.
abstract: Various mutations in the genes encoding alpha spectrin (SPTA1) or beta spectrin (SPTB) are known to cause erythrocyte membrane disorders, sometimes associated with severe neonatal jaundice and anemia. We used a next-generation sequencing panel to evaluate 3 unrelated neonates who had puzzling cases of nonimmune hemolytic jaundice. In each case, we identified novel mutations in either SPTA1 or SPTB. Correlating erythrocyte morphology, clinical course, and computational analysis, we submit that each of the 3 variants is a probable pathogenic cause of the hereditary hemolytic conditions in these patients. We hope other pediatric practitioners caring for neonates with what appears to be idiopathic severe neonatal hyperbilirubinemia will look for spectrin variants as a possible cause, because additional cases with these specific variants along with this clinical phenotype are needed to confirm our postulate that these 3 cases are indeed pathogenic mutations.
authors.affiliation: 1 University of Utah, Salt Lake City, UT, USA.|2 Intermountain Healthcare, Salt Lake City, UT, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Christensen
authors.affiliation: 1 University of Utah, Salt Lake City, UT, USA.|3 ARUP Laboratories, Salt Lake City, UT, USA.
authors.forename: Archana M
authors.initials: AM
authors.lastname: Agarwal
authors.affiliation: 1 University of Utah, Salt Lake City, UT, USA.
authors.forename: Hassan M
authors.initials: HM
authors.lastname: Yaish
authors.affiliation: 1 University of Utah, Salt Lake City, UT, USA.|3 ARUP Laboratories, Salt Lake City, UT, USA.
authors.forename: N Scott
authors.initials: NS
authors.lastname: Reading
authors.affiliation: 1 University of Utah, Salt Lake City, UT, USA.|2 Intermountain Healthcare, Salt Lake City, UT, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: O'Brien
authors.affiliation: 1 University of Utah, Salt Lake City, UT, USA.|3 ARUP Laboratories, Salt Lake City, UT, USA.|4 Salt Lake VA Hospital, Salt Lake City, UT, USA.
authors.forename: Josef T
authors.initials: JT
authors.lastname: Prchal
mesh_terms: D000328:Adult; D004612:Elliptocytosis, Hereditary / Q000150:complications / Q000235:genetics*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007567:Jaundice, Neonatal / Q000150:complications / Q000235:genetics* / Q000628:therapy; D008297:Male; D009154:Mutation / Q000235:genetics*; D010789:Phototherapy; D013049:Spectrin / Q000235:genetics*; D013103:Spherocytosis, Hereditary / Q000150:complications*
chemical_list: D013049:Spectrin
keywords: anemia; elliptocytosis; hyperbilirubinemia; spectrin; spherocytosis