Molecular screening of ADAMTSL2 gene in 33 patients reveals the genetic heterogeneity of geleophysic dysplasia
Journal of medical genetics, 2011•jmg.bmj.com
Background Geleophysic dysplasia (GD, OMIM 231050) is an autosomal recessive disorder
characterised by short stature, small hands and feet, stiff joints, and thick skin. Patients often
present with a progressive cardiac valvular disease which can lead to an early death. In a
previous study including six GD families, we have mapped the disease gene on
chromosome 9q34. 2 and identified mutations in the A Disintegrin And Metalloproteinase
with Thrombospondin repeats-like 2 gene (ADAMTSL2). Methods Following this study, we …
characterised by short stature, small hands and feet, stiff joints, and thick skin. Patients often
present with a progressive cardiac valvular disease which can lead to an early death. In a
previous study including six GD families, we have mapped the disease gene on
chromosome 9q34. 2 and identified mutations in the A Disintegrin And Metalloproteinase
with Thrombospondin repeats-like 2 gene (ADAMTSL2). Methods Following this study, we …
Background
Geleophysic dysplasia (GD, OMIM 231050) is an autosomal recessive disorder characterised by short stature, small hands and feet, stiff joints, and thick skin. Patients often present with a progressive cardiac valvular disease which can lead to an early death. In a previous study including six GD families, we have mapped the disease gene on chromosome 9q34.2 and identified mutations in the A Disintegrin And Metalloproteinase with Thrombospondin repeats-like 2 gene (ADAMTSL2).
Methods
Following this study, we have collected the samples of 30 additional GD families, including 33 patients and identified ADAMTSL2 mutations in 14/33 patients, comprising 13 novel mutations. The absence of mutation in 19 patients prompted us to compare the two groups of GD patients, namely group 1, patients with ADAMTSL2 mutations (n=20, also including the 6 patients from our previous study), and group 2, patients without ADAMTSL2 mutations (n=19).
Results
The main discriminating features were facial dysmorphism and tip-toe walking, which were almost constantly observed in group 1. No differences were found concerning heart involvement, skin thickness, recurrent respiratory and ear infections, bronchopulmonary insufficiency, laryngo-tracheal stenosis, deafness, and radiographic features.
Conclusions
It is concluded that GD is a genetically heterogeneous condition. Ongoing studies will hopefully lead to the identification of another disease gene.
jmg.bmj.com
