Homozygous SHOX gene deletion detected by array CGH in a girl with langer mesomelic dysplasia

Karaman B. , Satkın N., Altunoğlu U., Toksoy G. , Kayserili Karabay H., Uyguner Z. O. , ...More

European Human Genetics Conference 2014, Milan, Italy, 31 May - 03 June 2014, vol.22, no.1, pp.404

  • Publication Type: Conference Paper / Summary Text
  • Volume: 22
  • City: Milan
  • Country: Italy
  • Page Numbers: pp.404


Langer mesomelic dysplasia (LMD) is characterized by hypomelia with severe

hypoplasia of ulnae and 􀏐ibulae, and bowed, thickened radii and tibiae,

causing deformities of the hands and feet. LMD is caused by homozygous

mutations in the SHOX/SHOXY (short stature homoebox) gene, of which

heterozygous mutations or deletions cause Leri-Weil Dysplasia (LWD).

Phenotype of LWD can be incomplete between and within families. We present

a 13 year old female with LMD, the second child of healthy 􀏐irst cousin

parents. She had micrognathia, disproportionate short stature with various

musculoskeletal 􀏐indings (absence of the distal 􀏐lexion creases of the 3rd,

4th, 5th 􀏐ingers on the right, camptodactyly of the 3rd, 4th, 5th 􀏐ingers on

the left, tibial bowing). X-rays revealed hypoplasia of ulnae, 􀏐ibulae and the

mandible. Chromosome analysis and FISH investigation by using SHOX gene

probe revealed normal results. Sequence analysis failed due to unsuccessful

PCR ampli􀏐ications. Array comparative genomic hybridization (a-CGH) study

showed a 174 kb homozygous deletion, encompassing the SHOX gene.

Proband‘s parents were heterozygous for the same deletion by a-CGH. FISH

was uninformative, because there was no difference between the intensity

of the signals on both chromosomes. Since the primers used were located

within the deleted region, molecular studies could not be performed. A-CGH

proved to be the most powerful diagnostic tool in this case.