A 2-bp deletion mutation in
Niemann–Pick disease
SMPD1
imprint
Journal
Journal of pediatric endocrinology & metabolism : JPEM
ISSN: 2191-0251
Titre abrégé: J Pediatr Endocrinol Metab
Pays: Germany
ID NLM: 9508900
Informations de publication
Date de publication:
26 Aug 2022
26 Aug 2022
Historique:
received:
19
07
2021
accepted:
30
03
2022
pubmed:
27
5
2022
medline:
13
8
2022
entrez:
26
5
2022
Statut:
epublish
Résumé
Niemann-Pick disease type A (NPDA, MIM: 257200) is an autosomal recessive sphingolipidosis caused by lysosomal acid sphingomyelinase (ASM) deficiency. A cluster of genes located at chromosome 11p15 have been reported to be imprinted genes, such as TSSC5, TSSC3, and ZNF215 that flanking SMPD1 gene. It was reported by a few recent studies that SMPD1 gene was paternally imprinted and maternally preferentially expressed. A five-month-old boy with severe anemia, hepatosplenomegly and bone marrow foam cells was recruited from a complete cousin couple. To determine whether boy suffered from NPDA, ASM activity and SMPD1 gene sequencing were performed on available individuals of this pedigree including the proband, his parents and sister. The ASM activities of proband and parents showed deficiency (17.7 nmol/h/g-protein) and about 50% decreased (83.3 nmol/h/g-protein), respectively, compared with normal controls (204.5 nmol/h/g-protein). SMPD1 gene sequencing in the proband revealed a homozygous mutation c.1420_1421del, which leads to an open reading frameshift and a premature stop codon. The parents and some individuals of this family demonstrated heterozygous mutation at this locus. To investigate whether SMPD1 gene is imprinted as reported previously, the expression of RNA level was studied in the whole family members available. The members with heterozygous mutation for c.1420_1421del showed that both paternal and maternal inherited alleles were expressed. This study reported a c.1420_1421del mutation in SMPD1 gene which caused ASM activity decrease and this locus was biallelically expressed in heterozygous subjects implicating SMPD1 is not imprinted in this family.
Identifiants
pubmed: 35617710
pii: jpem-2021-0480
doi: 10.1515/jpem-2021-0480
doi:
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
1113-1116Informations de copyright
© 2022 Walter de Gruyter GmbH, Berlin/Boston.
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