MANDIBULOACRAL DYSPLASIA

ZMPSTE24 AND LMNA GENE ANALYSIS

Mandibuloacral dysplasia (MAD; OMIM 248370) is a rare autosomal recessive disorder characterized by skeletal abnormalities such as hypoplasia of the mandible and clavicles, acro-osteolysis of terminal phalanges, delayed closure of cranial sutures, joint contractures, mottled pigmentation, cutaneous atrophy, lipodystrophy and features of metabolic syndrome such as insulin resistance, hyperlipidaemia and diabetes. MAD shows considerable overlap with Hutchinson-Gilford progeria syndrome (HGPS) and familial partial lipodystrophy (FPLD).

Two genetically distinct subtypes are known for MAD: The MAD subtype A (MADA) caused by variants in lamin A/C (LMNA), encoding structural nuclear lamina proteins (see review by Garavelli et al 2009 Am J Med Genet A 149A, 2258-64) and the MAD subtype B (MADB) caused by variants in zinc metalloproteinase (ZMPSTE24), encoding an enzyme necessary for the correct processing and maturation of lamin A, an intermediate filament component of the nuclear envelope (see review by Ahmad et al 2010 Am J Med Genet A 152A, 2703-10).

The laboratory participates in the European Molecular Genetics Quality Network (EMQN) sequencing scheme.