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. 1. Introduction Mandibuloacral dysplasia (MAD) is a rare autosomal recessive disorder characterized by postnatal growth retardation, craniofacial anomalies, skeletal malformations, and mottled cutaneous pigmentation [1, 2]. Hutchinson-Gilford Progeria Syndrome (HGPS) is an autosomal dominant disorder demonstrating varying symptoms including short stature, hair loss, joint degeneration, and atherosclerosis [3]. Pathogenic mutations in the LMNA gene on chromosome 1q22 and encoding the Lamin A/C protein have been reported in both MAD and HGPS. To date, the majority of cases of MAD are caused by missense mutations in exons 8–10 of the LMNA gene [4, 5] that codes for the LAP2 and emerin-binding domain of the Lamin A/C protein. Recently, we encountered a two-year-old boy with overlapping features of MAD and HGPS. LMNA sequence analysis was performed to determine the genetic cause of his clinical phenotype. With the aim of identifying the molecular etiology of this boy’s phenotype, a comprehensive study was performed on the patient and parents. 2. Materials and Methods 2.1. LMNA Sequence Analysis The 12 coding exons plus exon-intron boundaries of the LMNA gene were amplified by polymerase chain reaction (PCR). The purified PCR products were sequenced in both directions using ABI Big Dye terminator mix (Life Technologies, Foster City, CA). Data were analyzed using Mutation Surveyor 3.20 software (SoftGenetics, LLC, PA). 2.2. LMNA Deletion Analysis by Real-Time Quantitative-PCR Real-time quantitative-PCR (RT-qPCR) was
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