Hutchinson-Gilford progeria syndrome is an autosomal dominant condition, which presents in early childhood with symptoms of premature aging and early death. The allelic disorder, mandibuloacral dysplasia is a disorder with progeroid facial appearance, mandibular hypoplasia and acro-osteolysis. These two diseases have been considered different clinical entities based on differences in phenotype and inheritance pattern but are both due to mutations in the lamin A/C (LMNA) gene. Differentiating the diseases clinically can be difficult due to their overlapping features and yet has important life expectancy implications as well as vastly different genetic counseling requirements. Our patient presents with a mixed clinical picture. The desire for diagnostic certainty is not only to understand his prognosis but also to determine the risk to his siblings and assist in family planning. Based on the clinical overlap between the Hutchinson-Gilford progeria syndrome and mandibuloacral dysplasia, we analyzed the LMNA gene in this patient. When a heterozygous change was identified, the parents were analyzed for the mutation. Deoxyribonucleic acid analysis for the LMNA gene revealed a heterozygous G to A change at nucleotide 412 in exon 2 of the LMNA gene resulting in replacement of glutamic acid with lysine at codon 138 (412 G>A; glu138lys). Neither parent had a mutation. Our results show that codon 138 (412 G>A; glu138lys) is a newly identified mutation of LMNA gene that results in a progeroid syndrome which is phenotypically similar to mandibuloacral dysplasia.
- Lamin A/C
- Mandibuloacral dysplasia
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Clinical Neurology