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

Abstract

Langer mesomelic dysplasia (LMD) is characterized by hypomelia with severehypoplasia of ulnae and ����ibulae, and bowed, thickened radii and tibiae,causing deformities of the hands and feet. LMD is caused by homozygousmutations in the SHOX/SHOXY (short stature homoebox) gene, of whichheterozygous mutations or deletions cause Leri-Weil Dysplasia (LWD).Phenotype of LWD can be incomplete between and within families. We presenta 13 year old female with LMD, the second child of healthy ����irst cousinparents. She had micrognathia, disproportionate short stature with variousmusculoskeletal ����indings (absence of the distal ����lexion creases of the 3rd,4th, 5th ����ingers on the right, camptodactyly of the 3rd, 4th, 5th ����ingers onthe left, tibial bowing). X-rays revealed hypoplasia of ulnae, ����ibulae and themandible. Chromosome analysis and FISH investigation by using SHOX geneprobe revealed normal results. Sequence analysis failed due to unsuccessfulPCR ampli����ications. Array comparative genomic hybridization (a-CGH) studyshowed a 174 kb homozygous deletion, encompassing the SHOX gene.Proband‘s parents were heterozygous for the same deletion by a-CGH. FISHwas uninformative, because there was no difference between the intensityof the signals on both chromosomes. Since the primers used were locatedwithin the deleted region, molecular studies could not be performed. A-CGHproved to be the most powerful diagnostic tool in this case.