Mandibuloacral Dysplasia Caused by LMNA Mutations and Uniparental Disomy
Figure 3
Uniparental disomy analysis of chromosome 1 and schematic representation of the generation of the homozygous p.M540T mutation. (a) Markers around the region of the LMNA gene in 1q22 show maternal isodisomy. Allele sizes for each marker are indicated. Informative markers for maternal UPD are denoted with an asterisk (*). Based on the results, one recombination event could have occurred proximal to D1S189 at 1p13.1 and a second recombination event could have occurred proximal to D1S213 at 1q41 resulting in maternal isodisomy for the 1q21-q22 region where the LMNA resides. Due to the uninformative nature of markers D1S2747, D1S2696, D1S2635, and D1S249 in the mother, it is unclear whether these regions are isodisomic or heterodisomic. The uninformative markers are indicated with question marks. (b) Schematic representation of the generation of the homozygous p.M540T mutation in the patient by the process of recombination and nondisjunction in maternal meiosis followed by trisomy rescue. Nondisjunction is shown as occurring in meiosis II in this figure, but it could also have occurred in meiosis I; the microsatellite markers used could not distinguish between these two possibilities. The p.M540T mutation is indicated by the red bar on one of the maternal chromosome 1′s. Paternal chromosome 1 is indicated by the blue colored. LMNA gene is indicated by the red bar.
