Imprinting at the SMPD1 locus: implications for acid sphingomyelinase-deficient Niemann-Pick disease.

American Journal of Human Genetics
Calogera M SimonaroE H Schuchman

Abstract

Acid sphingomyelinase (ASM) is the lipid hydrolase that is deficient in types A and B Niemann-Pick disease (NPD). Here, we demonstrate that the gene encoding ASM (SMPD1) is paternally imprinted and that differential expression of the mutant alleles in patients with ASM-deficient NPD and in carriers influences the disease phenotype. Comparison of the results of genomic sequencing versus reverse-transcriptase polymerase chain reaction sequencing for several patients with NPD revealed preferential expression of one mutant allele. Further analysis of one family showed that the expressed allele was maternally inherited and that the distinct clinical presentations of the individual patients were correlated with the amount of residual ASM activity expressed from the maternal mutation. Treatment of NPD cell lines with 5-aza-2'-deoxycytidine enhanced the expression of the paternal SMPD1 allele, and bisulfite genomic sequencing identified which CpG dinucleotides within the SMPD1 promoter were methylated. In a related set of studies, we identified a carrier individual who had approximately 15% of normal ASM activity and clinical features of ASM-deficient NPD. DNA sequencing confirmed that this individual carried a single SMPD1 mutation an...Continue Reading

Citations

Jul 17, 2007·Journal of Inherited Metabolic Disease·E H Schuchman
Oct 22, 2008·Journal of Inherited Metabolic Disease·Johannes Zschocke
Jun 24, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Eric L Smith, Edward H Schuchman
Mar 10, 2010·Journal of Lipid Research·You-Hai XuGregory A Grabowski
Mar 5, 2016·Molecular Genetics and Metabolism Reports·Wei-Lien ChuangKate Zhang
Oct 5, 2014·Journal of Hepatology·Carmen Garcia-RuizJosé C Fernández-Checa
Feb 7, 2017·Molecular Genetics and Metabolism·Edward H Schuchman, Robert J Desnick
Feb 24, 2017·Orphanet Journal of Rare Diseases·Margaret M McGovernOlivier Lidove
Jun 8, 2018·Journal of Inherited Metabolic Disease·Jean-Marie Saudubray, Fanny Mochel
Nov 28, 2019·International Journal of Molecular Sciences·Renato Santos, Olga Amaral
Jun 19, 2020·International Journal of Molecular Sciences·Vidyani SuryadevaraViswanathan Natarajan
Feb 24, 2020·Molecular Genetics and Metabolism·Eline C B EskesCarla E M Hollak
Aug 12, 2020·Anales de pediatría : publicación oficial de la Asociación Española de Pediatría (A.E.P.)·Pablo Del Villar-GuerraJorge J Cebolla
Feb 16, 2021·Molecular Biology and Evolution·Joshua H T PotterStephen J Rossiter
Aug 25, 2021·Molecular Biology and Evolution·Joshua H T PotterStephen J Rossiter
Apr 23, 2009·Cellular Signalling·Russell W JenkinsYusuf A Hannun
Sep 18, 2017·Molecular Genetics and Metabolism·Shahzeb HassanNahid Tayebi
Oct 18, 2007·Current Opinion in Endocrinology, Diabetes, and Obesity

❮ Previous
Next ❯

Related Concepts

Related Feeds

Beckwith-Wiedemann syndrome

Beckwith-Wiedemann syndrome is an imprinting disorder characterized by overgrowth, congenital malformations and predisposition to tumors. Discover the latest research on Beckwith-Wiedemann Syndrome here.