Affiliations: Division of Child and Adolescent Neurology,
Departments of Neurology and Pediatrics and Adolescent Medicine, Mayo College
of Medicine, Rochester, MN, USA | Department of Radiology, Mayo College of Medicine,
Rochester, MN, USA | Department of Medical Genetics, Mayo College of
Medicine, Rochester, MN, USA
Note: [] Correspondence: Dusica Babovic-Vuksanovic, M.D., Department of
Medical Genetics, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Tel.: +1 507 266 2967; Fax: +1 507 284 1067; E-mail: [email protected]
Abstract: 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.
