Two Decades after Mandibuloacral Dysplasia Discovery: Additional Cases and Comprehensive View of Disease Characteristics
Pathogenic variants in the <i>LMNA</i> gene cause a group of heterogeneous genetic disorders, called laminopathies. In particular, homozygous or compound heterozygous variants in <i>LMNA</i> have been associated with “mandibuloacral dysplasia type A” (MADA), an autosomal rece...
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MDPI AG
2021-09-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/10/1508 |
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| author | Isabelle Jéru Amira Nabil Gehad El-Makkawy Olivier Lascols Corinne Vigouroux Ebtesam Abdalla |
| author_facet | Isabelle Jéru Amira Nabil Gehad El-Makkawy Olivier Lascols Corinne Vigouroux Ebtesam Abdalla |
| author_sort | Isabelle Jéru |
| collection | DOAJ |
| description | Pathogenic variants in the <i>LMNA</i> gene cause a group of heterogeneous genetic disorders, called laminopathies. In particular, homozygous or compound heterozygous variants in <i>LMNA</i> have been associated with “mandibuloacral dysplasia type A” (MADA), an autosomal recessive disorder, characterized by mandibular hypoplasia, growth retardation mainly postnatal, pigmentary skin changes, progressive osteolysis of the distal phalanges and/or clavicles, and partial lipodystrophy. The detailed characteristics of this multisystemic disease have yet to be specified due to its rarity and the limited number of cases described. Here, we report three unrelated Egyptian patients with variable severity of MAD features. Next-generation sequencing using a gene panel revealed a homozygous c.1580G>A-p.Arg527His missense variant in <i>LMNA</i> exon 9 in an affected individual with a typical MADA phenotype. Another homozygous c.1580G>T-p.Arg527Leu variant affecting the same amino acid was identified in two additional patients, who both presented with severe manifestations very early in life. We combined our observations together with data from all MADA cases reported in the literature to get a clearer picture of the phenotypic variability in this disease. This work raises the number of reported MADA families, argues for the presence of the founder effect in Egypt, and strengthens genotype–phenotype correlations. |
| first_indexed | 2024-03-10T06:32:41Z |
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| id | doaj.art-5cdad722a2dc4bf2bac9c5b24b6cded5 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T06:32:41Z |
| publishDate | 2021-09-01 |
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| record_format | Article |
| series | Genes |
| spelling | doaj.art-5cdad722a2dc4bf2bac9c5b24b6cded52023-11-22T18:21:02ZengMDPI AGGenes2073-44252021-09-011210150810.3390/genes12101508Two Decades after Mandibuloacral Dysplasia Discovery: Additional Cases and Comprehensive View of Disease CharacteristicsIsabelle Jéru0Amira Nabil1Gehad El-Makkawy2Olivier Lascols3Corinne Vigouroux4Ebtesam Abdalla5Inserm UMR_S938, Saint-Antoine Research Center, Institute of Cardiometabolism and Nutrition, Sorbonne University, 75012 Paris, FranceDepartment of Human Genetics, Medical Research Institute, Alexandria University, Alexandria 21561, EgyptDepartment of Human Genetics, Medical Research Institute, Alexandria University, Alexandria 21561, EgyptInserm UMR_S938, Saint-Antoine Research Center, Institute of Cardiometabolism and Nutrition, Sorbonne University, 75012 Paris, FranceInserm UMR_S938, Saint-Antoine Research Center, Institute of Cardiometabolism and Nutrition, Sorbonne University, 75012 Paris, FranceDepartment of Human Genetics, Medical Research Institute, Alexandria University, Alexandria 21561, EgyptPathogenic variants in the <i>LMNA</i> gene cause a group of heterogeneous genetic disorders, called laminopathies. In particular, homozygous or compound heterozygous variants in <i>LMNA</i> have been associated with “mandibuloacral dysplasia type A” (MADA), an autosomal recessive disorder, characterized by mandibular hypoplasia, growth retardation mainly postnatal, pigmentary skin changes, progressive osteolysis of the distal phalanges and/or clavicles, and partial lipodystrophy. The detailed characteristics of this multisystemic disease have yet to be specified due to its rarity and the limited number of cases described. Here, we report three unrelated Egyptian patients with variable severity of MAD features. Next-generation sequencing using a gene panel revealed a homozygous c.1580G>A-p.Arg527His missense variant in <i>LMNA</i> exon 9 in an affected individual with a typical MADA phenotype. Another homozygous c.1580G>T-p.Arg527Leu variant affecting the same amino acid was identified in two additional patients, who both presented with severe manifestations very early in life. We combined our observations together with data from all MADA cases reported in the literature to get a clearer picture of the phenotypic variability in this disease. This work raises the number of reported MADA families, argues for the presence of the founder effect in Egypt, and strengthens genotype–phenotype correlations.https://www.mdpi.com/2073-4425/12/10/1508mandibuloacral dysplasia<i>LMNA</i>genotype–phenotype correlationlipodystrophyacro-osteolysis |
| spellingShingle | Isabelle Jéru Amira Nabil Gehad El-Makkawy Olivier Lascols Corinne Vigouroux Ebtesam Abdalla Two Decades after Mandibuloacral Dysplasia Discovery: Additional Cases and Comprehensive View of Disease Characteristics Genes mandibuloacral dysplasia <i>LMNA</i> genotype–phenotype correlation lipodystrophy acro-osteolysis |
| title | Two Decades after Mandibuloacral Dysplasia Discovery: Additional Cases and Comprehensive View of Disease Characteristics |
| title_full | Two Decades after Mandibuloacral Dysplasia Discovery: Additional Cases and Comprehensive View of Disease Characteristics |
| title_fullStr | Two Decades after Mandibuloacral Dysplasia Discovery: Additional Cases and Comprehensive View of Disease Characteristics |
| title_full_unstemmed | Two Decades after Mandibuloacral Dysplasia Discovery: Additional Cases and Comprehensive View of Disease Characteristics |
| title_short | Two Decades after Mandibuloacral Dysplasia Discovery: Additional Cases and Comprehensive View of Disease Characteristics |
| title_sort | two decades after mandibuloacral dysplasia discovery additional cases and comprehensive view of disease characteristics |
| topic | mandibuloacral dysplasia <i>LMNA</i> genotype–phenotype correlation lipodystrophy acro-osteolysis |
| url | https://www.mdpi.com/2073-4425/12/10/1508 |
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