A homozygous missense variant of SUMF1 in the Bedouin population extends the clinical spectrum in ultrarare neonatal multiple sulfatase deficiency
Abstract Background Multiple sulfatase deficiency (MSD, MIM #272200) is an ultrarare congenital disorder caused by SUMF1 mutation and often misdiagnosed due to its complex clinical presentation. Impeded by a lack of natural history, knowledge gained from individual case studies forms the source for...
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Wiley
2020-09-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.1167 |
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doaj-c0e977ea366f4c608dd81fe9e0b605482020-11-25T03:35:50ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-09-0189n/an/a10.1002/mgg3.1167A homozygous missense variant of SUMF1 in the Bedouin population extends the clinical spectrum in ultrarare neonatal multiple sulfatase deficiencyOrna Staretz‐Chacham0Lars Schlotawa1Ohad Wormser2Inbal Golan‐Tripto3Ohad S. Birk4Carlos R. Ferreira5Thomas Dierks6Karthikeyan Radhakrishnan7Metabolic Clinic Soroka University Medical Center Ben Gurion University Beer Sheva IsraelDepartment of Paediatrics and Adolescent Medicine University Medical Center Goettingen GermanyThe Morris Kahn Laboratory of Human Genetics National Institute for Biotechnology in the Negev and Faculty of Health Sciences Ben Gurion University of the Negev Beer Sheva IsraelDivision of Pediatrics Soroka University Medical Center Ben Gurion University Beer Sheva IsraelThe Morris Kahn Laboratory of Human Genetics National Institute for Biotechnology in the Negev and Faculty of Health Sciences Ben Gurion University of the Negev Beer Sheva IsraelMedical Genomics and Metabolic Genetics Branch National Human Genome Research Institute National Institutes of Health Bethesda MD USABiochemistry I Faculty of Chemistry Bielefeld University Bielefeld GermanyBiochemistry I Faculty of Chemistry Bielefeld University Bielefeld GermanyAbstract Background Multiple sulfatase deficiency (MSD, MIM #272200) is an ultrarare congenital disorder caused by SUMF1 mutation and often misdiagnosed due to its complex clinical presentation. Impeded by a lack of natural history, knowledge gained from individual case studies forms the source for a reliable diagnosis and consultation of patients and parents. Methods We collected clinical records as well as genetic and metabolic test results from two MSD patients. The functional properties of a novel SUMF1 variant were analyzed after expression in a cell culture model. Results We report on two MSD patients—the first neonatal type reported in Israel—both presenting with this most severe manifestation of MSD. Our patients showed uniform clinical symptoms with persistent pulmonary hypertension, hypotonia, and dysmorphism at birth. Both patients were homozygous for the same novel SUMF1 mutation (c.1043C>T, p.A348V). Functional analysis revealed that the SUMF1‐encoded variant of formylglycine‐generating enzyme is highly instable and lacks catalytic function. Conclusion The obtained results confirm genotype‒phenotype correlation in MSD, expand the spectrum of clinical presentation and are relevant for diagnosis including the extremely rare neonatal severe type of MSD.https://doi.org/10.1002/mgg3.1167deafnessdevelopmental delaydysmorphismformylglycine‐generating enzymehypotonialysosomal storage disorders |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Orna Staretz‐Chacham Lars Schlotawa Ohad Wormser Inbal Golan‐Tripto Ohad S. Birk Carlos R. Ferreira Thomas Dierks Karthikeyan Radhakrishnan |
| spellingShingle |
Orna Staretz‐Chacham Lars Schlotawa Ohad Wormser Inbal Golan‐Tripto Ohad S. Birk Carlos R. Ferreira Thomas Dierks Karthikeyan Radhakrishnan A homozygous missense variant of SUMF1 in the Bedouin population extends the clinical spectrum in ultrarare neonatal multiple sulfatase deficiency Molecular Genetics & Genomic Medicine deafness developmental delay dysmorphism formylglycine‐generating enzyme hypotonia lysosomal storage disorders |
| author_facet |
Orna Staretz‐Chacham Lars Schlotawa Ohad Wormser Inbal Golan‐Tripto Ohad S. Birk Carlos R. Ferreira Thomas Dierks Karthikeyan Radhakrishnan |
| author_sort |
Orna Staretz‐Chacham |
| title |
A homozygous missense variant of SUMF1 in the Bedouin population extends the clinical spectrum in ultrarare neonatal multiple sulfatase deficiency |
| title_short |
A homozygous missense variant of SUMF1 in the Bedouin population extends the clinical spectrum in ultrarare neonatal multiple sulfatase deficiency |
| title_full |
A homozygous missense variant of SUMF1 in the Bedouin population extends the clinical spectrum in ultrarare neonatal multiple sulfatase deficiency |
| title_fullStr |
A homozygous missense variant of SUMF1 in the Bedouin population extends the clinical spectrum in ultrarare neonatal multiple sulfatase deficiency |
| title_full_unstemmed |
A homozygous missense variant of SUMF1 in the Bedouin population extends the clinical spectrum in ultrarare neonatal multiple sulfatase deficiency |
| title_sort |
homozygous missense variant of sumf1 in the bedouin population extends the clinical spectrum in ultrarare neonatal multiple sulfatase deficiency |
| publisher |
Wiley |
| series |
Molecular Genetics & Genomic Medicine |
| issn |
2324-9269 |
| publishDate |
2020-09-01 |
| description |
Abstract Background Multiple sulfatase deficiency (MSD, MIM #272200) is an ultrarare congenital disorder caused by SUMF1 mutation and often misdiagnosed due to its complex clinical presentation. Impeded by a lack of natural history, knowledge gained from individual case studies forms the source for a reliable diagnosis and consultation of patients and parents. Methods We collected clinical records as well as genetic and metabolic test results from two MSD patients. The functional properties of a novel SUMF1 variant were analyzed after expression in a cell culture model. Results We report on two MSD patients—the first neonatal type reported in Israel—both presenting with this most severe manifestation of MSD. Our patients showed uniform clinical symptoms with persistent pulmonary hypertension, hypotonia, and dysmorphism at birth. Both patients were homozygous for the same novel SUMF1 mutation (c.1043C>T, p.A348V). Functional analysis revealed that the SUMF1‐encoded variant of formylglycine‐generating enzyme is highly instable and lacks catalytic function. Conclusion The obtained results confirm genotype‒phenotype correlation in MSD, expand the spectrum of clinical presentation and are relevant for diagnosis including the extremely rare neonatal severe type of MSD. |
| topic |
deafness developmental delay dysmorphism formylglycine‐generating enzyme hypotonia lysosomal storage disorders |
| url |
https://doi.org/10.1002/mgg3.1167 |
| work_keys_str_mv |
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