A new mutation in the CAVIN1/PTRF gene in two siblings with congenital generalized lipodystrophy type 4: case reports and review of the literature
Lipodystrophy syndromes are characterized by a progressive metabolic impairment secondary to adipose tissue dysfunction and may have a genetic background. Congenital generalized lipodystrophy type 4 (CGL4) is an extremely rare subtype, caused by mutations in the polymerase I and transcript release f...
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| Format: | Article |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1212729/full |
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| author | Valentina Mancioppi Tommaso Daffara Martina Romanisio Giovanni Ceccarini Caterina Pelosini Ferruccio Santini Simonetta Bellone Simonetta Bellone Simona Mellone Alessio Baricich Ivana Rabbone Gianluca Aimaretti Baris Akinci Mara Giordano Mara Giordano Flavia Prodam Flavia Prodam Flavia Prodam |
| author_facet | Valentina Mancioppi Tommaso Daffara Martina Romanisio Giovanni Ceccarini Caterina Pelosini Ferruccio Santini Simonetta Bellone Simonetta Bellone Simona Mellone Alessio Baricich Ivana Rabbone Gianluca Aimaretti Baris Akinci Mara Giordano Mara Giordano Flavia Prodam Flavia Prodam Flavia Prodam |
| author_sort | Valentina Mancioppi |
| collection | DOAJ |
| description | Lipodystrophy syndromes are characterized by a progressive metabolic impairment secondary to adipose tissue dysfunction and may have a genetic background. Congenital generalized lipodystrophy type 4 (CGL4) is an extremely rare subtype, caused by mutations in the polymerase I and transcript release factor (PTRF) gene. It encodes for a cytoplasmatic protein called caveolae-associated protein 1 (Cavin-1), which, together with caveolin 1, is responsible for the biogenesis of caveolae, being a master regulator of adipose tissue expandability. Cavin-1 is expressed in several tissues, including muscles, thus resulting, when dysfunctional, in a clinical phenotype characterized by the absence of adipose tissue and muscular dystrophy. We herein describe the clinical phenotypes of two siblings in their early childhood, with a phenotype characterized by a generalized reduction of subcutaneous fat, muscular hypertrophy, distinct facial features, myopathy, and atlantoaxial instability. One of the siblings developed paroxysmal supraventricular tachycardia leading to cardiac arrest at 3 months of age. Height and BMI were normal. Blood tests showed elevated CK, a mild increase in liver enzymes and triglycerides levels, and undetectable leptin and adiponectin concentrations. Fasting glucose and HbA1c were normal, while Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was mildly elevated. Both patients were hyperphagic and had cravings for foods rich in fats and sugars. Genetic testing revealed a novel pathogenic mutation of the CAVIN1/PTRF gene (NM_012232 exon1:c T21A:p.Y7X) at the homozygous state. The diagnosis of lipodystrophy can be challenging, often requiring a multidisciplinary approach, given the pleiotropic effect, involving several tissues. The coexistence of generalized lack of fat, myopathy with elevated CK levels, arrhythmias, gastrointestinal dysmotility, and skeletal abnormalities should prompt the suspicion for the diagnosis of CGL4, although phenotypic variability may occur. |
| first_indexed | 2024-03-13T00:06:25Z |
| format | Article |
| id | doaj.art-0a8266163f6e49a698c371cde0be45f3 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-13T00:06:25Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-0a8266163f6e49a698c371cde0be45f32023-07-13T00:01:55ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-07-011410.3389/fendo.2023.12127291212729A new mutation in the CAVIN1/PTRF gene in two siblings with congenital generalized lipodystrophy type 4: case reports and review of the literatureValentina Mancioppi0Tommaso Daffara1Martina Romanisio2Giovanni Ceccarini3Caterina Pelosini4Ferruccio Santini5Simonetta Bellone6Simonetta Bellone7Simona Mellone8Alessio Baricich9Ivana Rabbone10Gianluca Aimaretti11Baris Akinci12Mara Giordano13Mara Giordano14Flavia Prodam15Flavia Prodam16Flavia Prodam17Division of Pediatrics, Department of Health Sciences, University of Piemonte Orientale, Novara, ItalyEndocrinology, Department of Translational Medicine, University of Piemonte Orientale, Novara, ItalyEndocrinology, Department of Translational Medicine, University of Piemonte Orientale, Novara, ItalyObesity and Lipodystrophy Center, Endocrinology Unit, University Hospital of Pisa, Pisa, ItalyChemistry and Endocrinology Laboratory, Department of Laboratory Medicine, University Hospital of Pisa, Pisa, ItalyObesity and Lipodystrophy Center, Endocrinology Unit, University Hospital of Pisa, Pisa, ItalyDivision of Pediatrics, Department of Health Sciences, University of Piemonte Orientale, Novara, ItalyInterdisciplinary Research Center of Autoimmune and Allergic Diseases, University of Piemonte Orientale, Novara, ItalyLaboratory of Genetics, Struttura Complessa a Direzione Universitaria (SCDU) Biochimica Clinica, Ospedale Maggiore della Carità, Novara, ItalyPhysical Medicine and Rehabilitation, Department of Health Sciences, University of Piemonte Orientale, Novara, ItalyDivision of Pediatrics, Department of Health Sciences, University of Piemonte Orientale, Novara, ItalyEndocrinology, Department of Translational Medicine, University of Piemonte Orientale, Novara, ItalyDivision of Endocrinology and Metabolism, Faculty of Medicine, Dokuz Eylul University, Izmir, TürkiyeLaboratory of Genetics, Struttura Complessa a Direzione Universitaria (SCDU) Biochimica Clinica, Ospedale Maggiore della Carità, Novara, ItalyDepartment of Health Sciences, University of Piemonte Orientale, Novara, ItalyDivision of Pediatrics, Department of Health Sciences, University of Piemonte Orientale, Novara, ItalyEndocrinology, Department of Translational Medicine, University of Piemonte Orientale, Novara, ItalyInterdisciplinary Research Center of Autoimmune and Allergic Diseases, University of Piemonte Orientale, Novara, ItalyLipodystrophy syndromes are characterized by a progressive metabolic impairment secondary to adipose tissue dysfunction and may have a genetic background. Congenital generalized lipodystrophy type 4 (CGL4) is an extremely rare subtype, caused by mutations in the polymerase I and transcript release factor (PTRF) gene. It encodes for a cytoplasmatic protein called caveolae-associated protein 1 (Cavin-1), which, together with caveolin 1, is responsible for the biogenesis of caveolae, being a master regulator of adipose tissue expandability. Cavin-1 is expressed in several tissues, including muscles, thus resulting, when dysfunctional, in a clinical phenotype characterized by the absence of adipose tissue and muscular dystrophy. We herein describe the clinical phenotypes of two siblings in their early childhood, with a phenotype characterized by a generalized reduction of subcutaneous fat, muscular hypertrophy, distinct facial features, myopathy, and atlantoaxial instability. One of the siblings developed paroxysmal supraventricular tachycardia leading to cardiac arrest at 3 months of age. Height and BMI were normal. Blood tests showed elevated CK, a mild increase in liver enzymes and triglycerides levels, and undetectable leptin and adiponectin concentrations. Fasting glucose and HbA1c were normal, while Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was mildly elevated. Both patients were hyperphagic and had cravings for foods rich in fats and sugars. Genetic testing revealed a novel pathogenic mutation of the CAVIN1/PTRF gene (NM_012232 exon1:c T21A:p.Y7X) at the homozygous state. The diagnosis of lipodystrophy can be challenging, often requiring a multidisciplinary approach, given the pleiotropic effect, involving several tissues. The coexistence of generalized lack of fat, myopathy with elevated CK levels, arrhythmias, gastrointestinal dysmotility, and skeletal abnormalities should prompt the suspicion for the diagnosis of CGL4, although phenotypic variability may occur.https://www.frontiersin.org/articles/10.3389/fendo.2023.1212729/fulllipodystrophyCGL4PTRFadipose tissueleptinmuscular dystrophy |
| spellingShingle | Valentina Mancioppi Tommaso Daffara Martina Romanisio Giovanni Ceccarini Caterina Pelosini Ferruccio Santini Simonetta Bellone Simonetta Bellone Simona Mellone Alessio Baricich Ivana Rabbone Gianluca Aimaretti Baris Akinci Mara Giordano Mara Giordano Flavia Prodam Flavia Prodam Flavia Prodam A new mutation in the CAVIN1/PTRF gene in two siblings with congenital generalized lipodystrophy type 4: case reports and review of the literature Frontiers in Endocrinology lipodystrophy CGL4 PTRF adipose tissue leptin muscular dystrophy |
| title | A new mutation in the CAVIN1/PTRF gene in two siblings with congenital generalized lipodystrophy type 4: case reports and review of the literature |
| title_full | A new mutation in the CAVIN1/PTRF gene in two siblings with congenital generalized lipodystrophy type 4: case reports and review of the literature |
| title_fullStr | A new mutation in the CAVIN1/PTRF gene in two siblings with congenital generalized lipodystrophy type 4: case reports and review of the literature |
| title_full_unstemmed | A new mutation in the CAVIN1/PTRF gene in two siblings with congenital generalized lipodystrophy type 4: case reports and review of the literature |
| title_short | A new mutation in the CAVIN1/PTRF gene in two siblings with congenital generalized lipodystrophy type 4: case reports and review of the literature |
| title_sort | new mutation in the cavin1 ptrf gene in two siblings with congenital generalized lipodystrophy type 4 case reports and review of the literature |
| topic | lipodystrophy CGL4 PTRF adipose tissue leptin muscular dystrophy |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1212729/full |
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