title: Mandibuloacral Dysplasia Caused by LMNA Mutations and Uniparental Disomy.
abstract: Mandibuloacral dysplasia (MAD) is a rare autosomal recessive disorder characterized by postnatal growth retardation, craniofacial anomalies, skeletal malformations, and mottled cutaneous pigmentation. Hutchinson-Gilford Progeria Syndrome (HGPS) is characterized by the clinical features of accelerated aging in childhood. Both MAD and HGPS can be caused by mutations in the LMNA gene. In this study, we describe a 2-year-old boy with overlapping features of MAD and HGPS. Mutation analysis of the LMNA gene revealed a homozygous missense change, p.M540T, while only the mother carries the mutation. Uniparental disomy (UPD) analysis for chromosome 1 showed the presence of maternal UPD. Markers in the 1q21.3-q22 region flanking the LMNA locus were isodisomic, while markers in the short arm and distal 1q region were heterodisomic. These results suggest that nondisjunction in maternal meiosis followed by loss of the paternal chromosome 1 during trisomy rescue might result in the UPD1 and homozygosity for the p.M540T mutation observed in this patient.
authors.affiliation: University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
authors.forename: Shaochun
authors.initials: S
authors.lastname: Bai
authors.affiliation: University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Lozada
authors.affiliation: University of California and Children's Hospital of San Diego, San Diego, CA 92123, USA.
authors.forename: Marilyn C
authors.initials: MC
authors.lastname: Jones
authors.affiliation: Johns Hopkins University School of Medicine and Howard Hughes Medical Institute, Baltimore, MD 21287, USA.
authors.forename: Harry C
authors.initials: HC
authors.lastname: Dietz
authors.affiliation: University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Dempsey
authors.affiliation: University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA ; Department of Human Genetics, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
authors.forename: Soma
authors.initials: S
authors.lastname: Das