A Patient with Berardinelli-Seip Syndrome, Novel AGPAT2 Splicesite Mutation and Concomitant Development of Non-diabetic Polyneuropathy
Primary polyneuropathy in the context of Seip-Berardinelli type 1 seipinopathy, or congenital generalized lipodystrophy type 1 (CGL1) has not been previously reported. We report the case history of a 27 year old female CGL1 patient presenting with an unusual additional development of non-diabetic pe...
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| Format: | Article |
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Galenos Yayincilik
2019-09-01
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http://www.jcrpe.org/archives/archive-detail/article-preview/a-patient-with-berardinelli-seip-syndrome-novel-ia/20613
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| author | Joanna Oswiecimska Mateusz Dawidziuk Tomasz Gambin Katarzyna Ziora Marta Marek Sylwia Rzonca D. Lys Guilbride Shalini N. Jhangiani Anna Obuchowicz Alicja Sikora James R. Lupski Wojciech Wiszniewski Pawel Gawlinski |
| author_facet | Joanna Oswiecimska Mateusz Dawidziuk Tomasz Gambin Katarzyna Ziora Marta Marek Sylwia Rzonca D. Lys Guilbride Shalini N. Jhangiani Anna Obuchowicz Alicja Sikora James R. Lupski Wojciech Wiszniewski Pawel Gawlinski |
| author_sort | Joanna Oswiecimska |
| collection | DOAJ |
| description | Primary polyneuropathy in the context of Seip-Berardinelli type 1 seipinopathy, or congenital generalized lipodystrophy type 1 (CGL1) has not been previously reported. We report the case history of a 27 year old female CGL1 patient presenting with an unusual additional development of non-diabetic peripheral neuropathy and learning disabilities in early adolescence. Whole exome sequencing (WES) of the patient genome identified a novel variant, homozygous for a 52 bp intronic deletion in the AGPAT2 locus, coding for 1-acylglycerol-3-phosphate O-acyltransferase 2, which is uniquely associated with CGL1 seipinopathies, with no molecular evidence for dual diagnosis. Functional studies using RNA isolated from patient peripheral blood leucocytes showed abnormal RNA splicing resulting in the loss of 25 amino acids from the patient AGPAT2 protein coding sequence. Stability and transcription levels for the misspliced AGPAT2 mRNA in our patient nonetheless remained normal. Any AGPAT2 protein produced in our patient is therefore likely to be dysfunctional. However, formal linkage of this deletion to the neuropathy observed remains to be shown. The classical clinical presentation of a patient with AGPAT2-associated lipodystrophy shows normal cognition and no development of polyneuropathy. Cognitive disabilities and polyneuropathy are features associated exclusively with clinical CGL type 2 arising from seipin (BSCL2) gene mutations. This case study suggests that in some genetic contexts, AGPAT2 mutations can also produce phenotypes with primary polyneuropathy. |
| first_indexed | 2024-04-10T14:20:31Z |
| format | Article |
| id | doaj.art-4821a089932b4c249ada1740274433f5 |
| institution | Directory Open Access Journal |
| issn | 1308-5727 1308-5735 |
| language | English |
| last_indexed | 2024-04-10T14:20:31Z |
| publishDate | 2019-09-01 |
| publisher | Galenos Yayincilik |
| record_format | Article |
| series | JCRPE |
| spelling | doaj.art-4821a089932b4c249ada1740274433f52023-02-15T16:09:20ZengGalenos YayincilikJCRPE1308-57271308-57352019-09-0111331932610.4274/jcrpe.galenos.2018.2018.022713049054A Patient with Berardinelli-Seip Syndrome, Novel AGPAT2 Splicesite Mutation and Concomitant Development of Non-diabetic PolyneuropathyJoanna Oswiecimska0Mateusz Dawidziuk1Tomasz Gambin2Katarzyna Ziora3Marta Marek4Sylwia Rzonca5D. Lys Guilbride6Shalini N. Jhangiani7Anna Obuchowicz8Alicja Sikora9James R. Lupski10Wojciech Wiszniewski11Pawel Gawlinski12 Medical University of Silesia in Katowice, Department of Pediatrics in Zabrze, Silesia, Poland Institute of Mother and Child, Department of Medical Genetics, Warsaw, Poland Institute of Mother and Child, Department of Medical Genetics, Warsaw, Poland Medical University of Silesia in Katowice, Department of Pediatrics in Zabrze, Silesia, Poland Medical University of Silesia in Katowice, Department of Pediatrics in Bytom, Silesia, Poland Institute of Mother and Child, Department of Medical Genetics, Warsaw, Poland No current affiliation Human Genome Sequencing Center, Baylor College of Medicine, Texas, USA Medical University of Silesia in Katowice, Department of Pediatrics in Bytom, Silesia, Poland Medical University of Silesia in Katowice, Department of Pediatrics in Bytom, Silesia, Poland Baylor College of Medicine, Department of Molecular and Human Genetics, Texas, USA Institute of Mother and Child, Department of Medical Genetics, Warsaw, Poland Institute of Mother and Child, Department of Medical Genetics, Warsaw, Poland Primary polyneuropathy in the context of Seip-Berardinelli type 1 seipinopathy, or congenital generalized lipodystrophy type 1 (CGL1) has not been previously reported. We report the case history of a 27 year old female CGL1 patient presenting with an unusual additional development of non-diabetic peripheral neuropathy and learning disabilities in early adolescence. Whole exome sequencing (WES) of the patient genome identified a novel variant, homozygous for a 52 bp intronic deletion in the AGPAT2 locus, coding for 1-acylglycerol-3-phosphate O-acyltransferase 2, which is uniquely associated with CGL1 seipinopathies, with no molecular evidence for dual diagnosis. Functional studies using RNA isolated from patient peripheral blood leucocytes showed abnormal RNA splicing resulting in the loss of 25 amino acids from the patient AGPAT2 protein coding sequence. Stability and transcription levels for the misspliced AGPAT2 mRNA in our patient nonetheless remained normal. Any AGPAT2 protein produced in our patient is therefore likely to be dysfunctional. However, formal linkage of this deletion to the neuropathy observed remains to be shown. The classical clinical presentation of a patient with AGPAT2-associated lipodystrophy shows normal cognition and no development of polyneuropathy. Cognitive disabilities and polyneuropathy are features associated exclusively with clinical CGL type 2 arising from seipin (BSCL2) gene mutations. This case study suggests that in some genetic contexts, AGPAT2 mutations can also produce phenotypes with primary polyneuropathy. http://www.jcrpe.org/archives/archive-detail/article-preview/a-patient-with-berardinelli-seip-syndrome-novel-ia/20613 Berardinelli-Seip syndromeseipinopathycongenital generalized lipodystrophypolyneuropathyAGPAT2fat biology |
| spellingShingle | Joanna Oswiecimska Mateusz Dawidziuk Tomasz Gambin Katarzyna Ziora Marta Marek Sylwia Rzonca D. Lys Guilbride Shalini N. Jhangiani Anna Obuchowicz Alicja Sikora James R. Lupski Wojciech Wiszniewski Pawel Gawlinski A Patient with Berardinelli-Seip Syndrome, Novel AGPAT2 Splicesite Mutation and Concomitant Development of Non-diabetic Polyneuropathy JCRPE Berardinelli-Seip syndrome seipinopathy congenital generalized lipodystrophy polyneuropathy AGPAT2 fat biology |
| title | A Patient with Berardinelli-Seip Syndrome, Novel AGPAT2 Splicesite Mutation and Concomitant Development of Non-diabetic Polyneuropathy |
| title_full | A Patient with Berardinelli-Seip Syndrome, Novel AGPAT2 Splicesite Mutation and Concomitant Development of Non-diabetic Polyneuropathy |
| title_fullStr | A Patient with Berardinelli-Seip Syndrome, Novel AGPAT2 Splicesite Mutation and Concomitant Development of Non-diabetic Polyneuropathy |
| title_full_unstemmed | A Patient with Berardinelli-Seip Syndrome, Novel AGPAT2 Splicesite Mutation and Concomitant Development of Non-diabetic Polyneuropathy |
| title_short | A Patient with Berardinelli-Seip Syndrome, Novel AGPAT2 Splicesite Mutation and Concomitant Development of Non-diabetic Polyneuropathy |
| title_sort | patient with berardinelli seip syndrome novel agpat2 splicesite mutation and concomitant development of non diabetic polyneuropathy |
| topic | Berardinelli-Seip syndrome seipinopathy congenital generalized lipodystrophy polyneuropathy AGPAT2 fat biology |
| url |
http://www.jcrpe.org/archives/archive-detail/article-preview/a-patient-with-berardinelli-seip-syndrome-novel-ia/20613
|
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