An inherited LMNA gene mutation in atypical Progeria syndrome

Authors

  • Yassamine Doubaj,

    Corresponding author
    1. Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohamed V, Rabat, Morocco
    2. Département de Génétique Médicale, Institut National d'Hygiène, Rabat, Morocco
    • Département de Génétique Médicale, Institut National d'Hygiène, 27, Avenue Ibn Batouta, BP 769, 11400 Rabat, Morocco.
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  • Annachiara De Sandre-Giovannoli,

    Corresponding author
    1. Laboratoire de Génétique Moléculaire, Département de Génétique Médicale et Biologie Cellulaire, Hôpital la Timone Enfants, Marseille, France
    2. Inserm UMR_S910 “Génétique Médicale et Génomique Fonctionnelle,” Faculté de Médecine la Timone, Marseille, France
    • Laboratoire de Génétique Moléculaire, Département de Génétique Médicale et Biologie Cellulaire, Hôpital la Timone Enfants, 264 Rue St Pierre, 13385 Marseille, France.
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  • Esteves-Vieira Vera,

    1. Laboratoire de Génétique Moléculaire, Département de Génétique Médicale et Biologie Cellulaire, Hôpital la Timone Enfants, Marseille, France
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  • Claire Laure Navarro,

    1. Inserm UMR_S910 “Génétique Médicale et Génomique Fonctionnelle,” Faculté de Médecine la Timone, Marseille, France
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  • Siham Chafai Elalaoui,

    1. Département de Génétique Médicale, Institut National d'Hygiène, Rabat, Morocco
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  • Mariam Tajir,

    1. Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohamed V, Rabat, Morocco
    2. Département de Génétique Médicale, Institut National d'Hygiène, Rabat, Morocco
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  • Nicolas Lévy,

    1. Laboratoire de Génétique Moléculaire, Département de Génétique Médicale et Biologie Cellulaire, Hôpital la Timone Enfants, Marseille, France
    2. Inserm UMR_S910 “Génétique Médicale et Génomique Fonctionnelle,” Faculté de Médecine la Timone, Marseille, France
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  • Abdelaziz Sefiani

    1. Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohamed V, Rabat, Morocco
    2. Département de Génétique Médicale, Institut National d'Hygiène, Rabat, Morocco
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  • How to Cite this Article: Doubaj Y, De Sandre-Giovannoli A, Vera E-V, Navarro CL, Elalaoui SC, Tajir M, Lévy N, Sefiani A. 2012. An inherited LMNA gene mutation in atypical progeria syndrome. Am J Med Genet Part A 158A: 2881–2887.

  • Y. Doubaj and A. De Sandre-Giovannoli contributed equally to this work.

Abstract

Hutchinson–Gilford Progeria syndrome (HGPS) is a rare genetic disorder, characterized by several clinical features that begin in early childhood, recalling an accelerated aging process. The diagnosis of HGPS is based on the recognition of common clinical features and detection of the recurrent heterozygous c.1824C>T (p.Gly608Gly) mutation within exon 11 in the Lamin A/C encoding gene (LMNA). Besides “typical HGPS,” several “atypical progeria” syndromes (APS) have been described, in a clinical spectrum ranging from mandibuloacral dysplasia to atypical Werner syndrome. These patients's clinical features include progeroid manifestations, such as short stature, prominent nose, premature graying of hair, partial alopecia, skin atrophy, lipodystrophy, skeletal anomalies, such as mandibular hypoplasia and acroosteolyses, and in some cases severe atherosclerosis with metabolic complications. APS are due in several cases to de novo heterozygous LMNA mutations other than the p.Gly608Gly, or due to homozygous BAFN1 mutations in Nestor–Guillermo Progeria syndrome (NGPS). We report here and discuss the observation of a non-consanguineous Moroccan patient presenting with atypical progeria. The molecular studies showed the heterozygous mutation c.412G>A (p.Glu138Lys) of the LMNA gene. This mutation, previously reported as a de novo mutation, was inherited from the apparently healthy father who showed a somatic cell mosaicism. © 2012 Wiley Periodicals, Inc.

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