title: An inherited LMNA gene mutation in atypical Progeria syndrome.
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.
authors.affiliation: Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohamed V, Rabat, Morocco. y.doubaj@gmail.com
authors.forename: Yassamine
authors.initials: Y
authors.lastname: Doubaj
authors.forename: Annachiara
authors.initials: A
authors.lastname: De Sandre-Giovannoli
authors.forename: Esteves-Vieira
authors.initials: EV
authors.lastname: Vera
authors.forename: Claire Laure
authors.initials: CL
authors.lastname: Navarro
authors.forename: Siham Chafai
authors.initials: SC
authors.lastname: Elalaoui
authors.forename: Mariam
authors.initials: M
authors.lastname: Tajir
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lévy
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Sefiani
mesh_terms: D001483:Base Sequence; D002648:Child; D005091:Exons; D017809:Fatal Outcome; D005260:Female; D006579:Heterozygote; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D011371:Progeria / Q000175:diagnosis / Q000235:genetics*
chemical_list: D034904:Lamin Type A