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Triangular tibia with fibular aplasia associated with a microdeletion on 2q11.2 encompassing LAF4.
- Source :
-
Clinical genetics [Clin Genet] 2008 Dec; Vol. 74 (6), pp. 560-5. Date of Electronic Publication: 2008 Jun 23. - Publication Year :
- 2008
-
Abstract
- Nievergelt syndrome (NS) is an autosomal dominant mesomelic dysplasia characterized by specific deformities of the radius, ulna, fibula and a rhomboid shape of the tibia. Phenotypically overlapping conditions such as mesomelic dysplasia, Savarirayan-type (MIM 605274), have been described, but their pathogenesis also remains unknown. We report on a girl with fibular agenesis, severely abnormal, triangular tibiae, urogenital tract malformations, failure to thrive, convulsions and recurrent apnoeas leading to respiratory arrest at the age of 4 months. Her skeletal findings correspond to those of the mesomelic dysplasia, Savarirayan-type recently described in two patients. In addition to the skeletal findings, our patient had central nervous system manifestations and developmental anomalies of the urogenital tract. In the patient described in this study, array comparative genomic hybridization (CGH) analysis revealed a de novo interstitial microdeletion of 500 kb on chromosome 2q11.1 containing the LAF4/AFF3 (lymphoid-nuclear-protein-related AF4) gene. In situ hybridization analysis of Laf4 in mouse embryos revealed expression in the developing brain, in the limb buds and in the zeugopod corresponding to the limb phenotype. Haploinsufficiency for LAF4/AFF3 is associated with limb, brain and urogenital malformations and specific changes of the tibia that are part of the NS spectrum.
- Subjects :
- Animals
Bone Diseases diagnostic imaging
Female
Fibula diagnostic imaging
Foot Deformities, Congenital genetics
Gene Expression Regulation, Developmental
Humans
In Situ Hybridization
Infant
Infant, Newborn
Mice
Radiography
Tibia diagnostic imaging
Bone Diseases genetics
Chromosome Deletion
Chromosomes, Human, Pair 2 genetics
Fibula abnormalities
Nuclear Proteins genetics
Tibia abnormalities
Subjects
Details
- Language :
- English
- ISSN :
- 1399-0004
- Volume :
- 74
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Clinical genetics
- Publication Type :
- Academic Journal
- Accession number :
- 18616733
- Full Text :
- https://doi.org/10.1111/j.1399-0004.2008.01050.x