Case report: The spectrum of SMPD1 pathogenic variants in Hungary
Acid sphingomyelinase deficiency (ASMD) is an autosomal recessive disease caused by biallelic pathogenic variants in the sphingomyelin phosphodiesterase-1 (SMPD1) gene. Acid sphingomyelinase deficiency is characterized by a spectrum of disease and is broadly divided into three types (ASMD type A, AS...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-06-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1158108/full |
| _version_ | 1797810486177169408 |
|---|---|
| author | Maria Judit Molnar Maria Judit Molnar Tamas Szlepak Tamas Szlepak Ildikó Csürke Szendile Loth Rita Káposzta Melinda Erdős Antal Dezsőfi |
| author_facet | Maria Judit Molnar Maria Judit Molnar Tamas Szlepak Tamas Szlepak Ildikó Csürke Szendile Loth Rita Káposzta Melinda Erdős Antal Dezsőfi |
| author_sort | Maria Judit Molnar |
| collection | DOAJ |
| description | Acid sphingomyelinase deficiency (ASMD) is an autosomal recessive disease caused by biallelic pathogenic variants in the sphingomyelin phosphodiesterase-1 (SMPD1) gene. Acid sphingomyelinase deficiency is characterized by a spectrum of disease and is broadly divided into three types (ASMD type A, ASMD type A/B, and ASMD type B). More than 220 disease-associated SMPD1 variants have been reported, and genotype/phenotype correlations are limited. Here we report the first description of all six diagnosed acid sphingomyelinase deficiency cases in Hungary. Nine SMPD1 variants are present in this cohort, including 3 SMPD1 variants (G247D, M384R, and F572L), which have only been described in Hungarian patients. All described variants are deemed to be pathogenic. Eight of the variants are missense, and one is a frameshift variant. The treatment of an ASMD type A/B patient in this cohort using hematopoietic stem cell transplantation is also detailed. This study may help to support diagnosis, patient genetic counseling, and management of acid sphingomyelinase deficiency. |
| first_indexed | 2024-03-13T07:08:34Z |
| format | Article |
| id | doaj.art-4e5af7abff8345f7874df2075855a40b |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-13T07:08:34Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-4e5af7abff8345f7874df2075855a40b2023-06-06T04:55:37ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-06-011410.3389/fgene.2023.11581081158108Case report: The spectrum of SMPD1 pathogenic variants in HungaryMaria Judit Molnar0Maria Judit Molnar1Tamas Szlepak2Tamas Szlepak3Ildikó Csürke4Szendile Loth5Rita Káposzta6Melinda Erdős7Antal Dezsőfi8Institute of Genomic Medicine and Rare Disorders, Semmelweis University, Budapest, HungaryELKH-SE Multiomics Neurodegeneration Research Group, Eötvös Loránd Research Network, Budapest, HungaryInstitute of Genomic Medicine and Rare Disorders, Semmelweis University, Budapest, HungaryELKH-SE Multiomics Neurodegeneration Research Group, Eötvös Loránd Research Network, Budapest, HungaryDepartment of Pediatrics, Josa Andras County Hospital, Nyiregyhaza, HungaryDepartment of Pediatrics, Semmelweis University, Budapest, HungaryDepartment of Pediatrics, University of Debrecen, Debrecen, HungaryPID Clinical Unit and Laboratory, Department of Dermatology, Venereology, and Dermatooncology, Semmelweis University, Budapest, HungaryDepartment of Pediatrics, Semmelweis University, Budapest, HungaryAcid sphingomyelinase deficiency (ASMD) is an autosomal recessive disease caused by biallelic pathogenic variants in the sphingomyelin phosphodiesterase-1 (SMPD1) gene. Acid sphingomyelinase deficiency is characterized by a spectrum of disease and is broadly divided into three types (ASMD type A, ASMD type A/B, and ASMD type B). More than 220 disease-associated SMPD1 variants have been reported, and genotype/phenotype correlations are limited. Here we report the first description of all six diagnosed acid sphingomyelinase deficiency cases in Hungary. Nine SMPD1 variants are present in this cohort, including 3 SMPD1 variants (G247D, M384R, and F572L), which have only been described in Hungarian patients. All described variants are deemed to be pathogenic. Eight of the variants are missense, and one is a frameshift variant. The treatment of an ASMD type A/B patient in this cohort using hematopoietic stem cell transplantation is also detailed. This study may help to support diagnosis, patient genetic counseling, and management of acid sphingomyelinase deficiency.https://www.frontiersin.org/articles/10.3389/fgene.2023.1158108/fullASMDacid sphingomyelinase deficiency type A/Bintermediate-type acid sphingomyelinase deficiencyNiemann-Pick disease type A/BSMPD1 |
| spellingShingle | Maria Judit Molnar Maria Judit Molnar Tamas Szlepak Tamas Szlepak Ildikó Csürke Szendile Loth Rita Káposzta Melinda Erdős Antal Dezsőfi Case report: The spectrum of SMPD1 pathogenic variants in Hungary Frontiers in Genetics ASMD acid sphingomyelinase deficiency type A/B intermediate-type acid sphingomyelinase deficiency Niemann-Pick disease type A/B SMPD1 |
| title | Case report: The spectrum of SMPD1 pathogenic variants in Hungary |
| title_full | Case report: The spectrum of SMPD1 pathogenic variants in Hungary |
| title_fullStr | Case report: The spectrum of SMPD1 pathogenic variants in Hungary |
| title_full_unstemmed | Case report: The spectrum of SMPD1 pathogenic variants in Hungary |
| title_short | Case report: The spectrum of SMPD1 pathogenic variants in Hungary |
| title_sort | case report the spectrum of smpd1 pathogenic variants in hungary |
| topic | ASMD acid sphingomyelinase deficiency type A/B intermediate-type acid sphingomyelinase deficiency Niemann-Pick disease type A/B SMPD1 |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1158108/full |
| work_keys_str_mv | AT mariajuditmolnar casereportthespectrumofsmpd1pathogenicvariantsinhungary AT mariajuditmolnar casereportthespectrumofsmpd1pathogenicvariantsinhungary AT tamasszlepak casereportthespectrumofsmpd1pathogenicvariantsinhungary AT tamasszlepak casereportthespectrumofsmpd1pathogenicvariantsinhungary AT ildikocsurke casereportthespectrumofsmpd1pathogenicvariantsinhungary AT szendileloth casereportthespectrumofsmpd1pathogenicvariantsinhungary AT ritakaposzta casereportthespectrumofsmpd1pathogenicvariantsinhungary AT melindaerdos casereportthespectrumofsmpd1pathogenicvariantsinhungary AT antaldezsofi casereportthespectrumofsmpd1pathogenicvariantsinhungary |