Details

Autor(en) / Beteiligte

• Novelli, Giuseppe
• Muchir, Antoine
• Sangiuolo, Federica
• Helbling-Leclerc, Anne
• D’Apice, Maria Rosaria
• Massart, Catherine
• Capon, Francesca
• Sbraccia, Paolo
• Federici, Massimo
• Lauro, Renato
• Tudisco, Cosimo
• Pallotta, Rosanna
• Scarano, Gioacchino
• Dallapiccola, Bruno
• Merlini, Luciano
• Bonne, Gisèle

Titel

Mandibuloacral Dysplasia Is Caused by a Mutation in LMNA-Encoding Lamin A/C

Ist Teil von

• American journal of human genetics, 2002-08, Vol.71 (2), p.426-431

Ort / Verlag

Chicago, IL: Elsevier Inc

Erscheinungsjahr

2002

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Mandibuloacral dysplasia (MAD) is a rare autosomal recessive disorder, characterized by postnatal growth retardation, craniofacial anomalies, skeletal malformations, and mottled cutaneous pigmentation. The LMNA gene encoding two nuclear envelope proteins (lamins A and C [lamin A/C]) maps to chromosome 1q21 and has been associated with five distinct pathologies, including Dunnigan-type familial partial lipodystrophy, a condition that is characterized by subcutaneous fat loss and is invariably associated with insulin resistance and diabetes. Since patients with MAD frequently have partial lipodystrophy and insulin resistance, we hypothesized that the disease may be caused by mutations in the LMNA gene. We analyzed five consanguineous Italian families and demonstrated linkage of MAD to chromosome 1q21, by use of homozygosity mapping. We then sequenced the LMNA gene and identified a homozygous missense mutation (R527H) that was shared by all affected patients. Patient skin fibroblasts showed nuclei that presented abnormal lamin A/C distribution and a dysmorphic envelope, thus demonstrating the pathogenic effect of the R527H LMNA mutation.