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Microdeletions on 6p22.3 are associated with mesomelic dysplasia Savarirayan type
- Source :
- Journal of Medical Genetics
- Publication Year :
- 2015
-
Abstract
- Introduction Mesomelic dysplasias are a group of skeletal disorders characterised by shortness of the middle limb segments (mesomelia). They are divided into 11 different categories. Among those without known molecular basis is mesomelic dysplasia Savarirayan type, characterised by severe shortness of the middle segment of the lower limb. Objective To identify the molecular cause of mesomelic dysplasia Savarirayan type. Methods and results We performed array comparative genomic hybridisation in three unrelated patients with mesomelic dysplasia Savarirayan type and identified 2 Mb overlapping de novo microdeletions on chromosome 6p22.3. The deletions encompass four known genes: MBOAT1 , E2F3, CDKAL1 and SOX4. All patients showed mesomelia of the lower limbs with hypoplastic tibiae and fibulae. We identified a fourth patient with intellectual disability and an overlapping slightly larger do novo deletion also encompassing the flanking gene ID4. Given the fact that the fourth patient had no skeletal abnormalities and none of the genes in the deleted interval are known to be associated with abnormalities in skeletal development, other mutational mechanisms than loss of function of the deleted genes have to be considered. Analysis of the genomic region showed that the deletion removes two regulatory boundaries and brings several potential limb enhancers into close proximity of ID4. Thus, the deletion could result in the aberrant activation and misexpression of ID4 in the limb bud, thereby causing the mesomelic dysplasia. Conclusions Our data indicate that the distinct deletion 6p22.3 is associated with mesomelic dysplasia Savarirayan type featuring hypoplastic, triangular-shaped tibiae and abnormally shaped or hypoplastic fibulae.
- Subjects :
- Molecular Sequence Data
Mesomelic Dysplasia
Ulna
Biology
Osteochondrodysplasias
Real-Time Polymerase Chain Reaction
SOXC Transcription Factors
Limb bud
Acetyltransferases
Mesomelia
Genetics
medicine
Humans
CDKAL1
Genetics (clinical)
Sequence Deletion
Chromosome Aberrations
Mesomelic dysplasia Savarirayan type
Comparative Genomic Hybridization
Leg
tRNA Methyltransferases
Base Sequence
Tibia
Membrane Proteins
Chromosome
Cyclin-Dependent Kinase 5
Sequence Analysis, DNA
medicine.disease
TRNA Methyltransferases
Radius
E2F3 Transcription Factor
Fibula
Chromosomes, Human, Pair 6
Inhibitor of Differentiation Proteins
Comparative genomic hybridization
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Journal of Medical Genetics
- Accession number :
- edsair.doi.dedup.....915a71735ddbab46ef8d8ca43a85967c