Association of homozygous LMNA mutation R471C with new phenotype: Mandibuloacral dysplasia, progeria, and rigid spine muscular dystrophy

We report on a 7‐year‐old girl with a phenotype combining mandibuloacral dysplasia (MAD), progeria, and rigid spine muscular dystrophy. Mild proximal weakness, contractures, and rigidity of the spine were the primary findings. Although present since birth, dysmorphic manifestations typical for MAD a...

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Published in:American journal of medical genetics. Part A 2008-04, Vol.146A (8), p.1049-1054
Main Authors: Zirn, Birgit, Kress, Wolfram, Grimm, Tiemo, Berthold, Lars Daniel, Neubauer, Bernd, Kuchelmeister, Klaus, Müller, Ulrich, Hahn, Andreas
Format: Article
Language:English
Subjects:
Biological and medical sciences
Child
Craniofacial Abnormalities - genetics
Craniofacial Abnormalities - physiopathology
Diseases of striated muscles. Neuromuscular diseases
Female
Homozygote
Humans
Lamin Type A - genetics
LMNA
mandibuloacral dysplasia
Medical genetics
Medical sciences
Muscular Dystrophies - genetics
Muscular Dystrophies - physiopathology
muscular dystrophy
Mutation
Neurology
Phenotype
progeria
Progeria - physiopathology
spinal rigidity
Spine - abnormalities
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Summary:We report on a 7‐year‐old girl with a phenotype combining mandibuloacral dysplasia (MAD), progeria, and rigid spine muscular dystrophy. Mild proximal weakness, contractures, and rigidity of the spine were the primary findings. Although present since birth, dysmorphic manifestations typical for MAD and progeroid features became more prominent with time, and the full clinical phenotype was recognizable at early school age. Her phenotype was caused by a homozygous mutation in LMNA (c.1411C > T, which predicts p.R471C) inherited from the heterozygous, consanguineous, unaffected parents. This mutation has only been reported in compound heterozygous state and was associated with a milder phenotype. Some LMNA mutations are known to cause MAD and overlapping phenotypes (MAD spectrum) in an autosomal recessive pattern. The p.R471C homozygous LMNA mutation causes a severe phenotype of the MAD spectrum. This case extends the clinical spectrum of MAD and further expands the phenotypic range of lamin A/C associated diseases. © 2008 Wiley‐Liss, Inc.
ISSN:1552-4825
1552-4833
DOI:10.1002/ajmg.a.32259