Distal acroosteolysis, poikiloderma and joint stiffness: a novel laminopathy?

Eur J Hum Genet 2016 08 6;24(8):1220-2. Epub 2016 Jan 6.

Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

LMNA encodes lamin A and lamin C, two major components of the nuclear lamina, and its pathogenic variants lead to a dozen distinct clinical entities collectively known as laminopathies. Most LMNA-related laminopathies are autosomal dominant but four are autosomal recessive; furthermore, some of the dominant variants have been associated with distinct phenotypes when inherited recessively, further complicating the ability to correlate genotype with phenotype. We report a consanguineous family in which the index presented with an apparently unique constellation of poikiloderma, joint motion restriction and distal acroosteolysis but lacks features of muscle weakness, lipodystrophy, or cardiac or craniofacial involvement. Molecular analysis revealed the presence of a novel homozygous LMNA missense variant (NM_170707.3:c.1774G>A; p.(Gly592Arg)) within an area of autozygome that is not shared by his unaffected siblings. The proposed causal link is further supported by in silico analysis of this variant. Our case suggests an expansion of LMNA allelic disorders to include distal acroosteolysis, poikiloderma and joint stiffness (DAPJ).

Download full-text PDF

Source
http://dx.doi.org/10.1038/ejhg.2015.265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970680PMC
August 2016

Publication Analysis

Top Keywords

poikiloderma joint
12
distal acroosteolysis
12
acroosteolysis poikiloderma
8
joint stiffness
8
report consanguineous
4
proposed causal
4
genotype phenotype
4
causal link
4
consanguineous family
4
phenotype report
4
presented unique
4
constellation poikiloderma
4
unaffected siblings
4
unique constellation
4
correlate genotype
4
family presented
4
siblings proposed
4
complicating ability
4
distinct phenotypes
4
phenotypes inherited
4

Similar Publications