Triangular tibia with fibular aplasia associated with a microdeletion on 2q11.2 encompassing LAF4.

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.
Authors	E Steichen-Gersdorf, I Gassner, A Superti-Furga, R Ullmann, S Stricker, E Klopocki, S Mundlos
Journal	Clinical genetics (Clin Genet) Vol. 74 Issue 6 Pg. 560-5 (Dec 2008) ISSN: 1399-0004 [Electronic] Denmark
PMID	18616733 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	AFF3 protein, human Nuclear Proteins
Topics	Animals Bone Diseases (diagnostic imaging, genetics) Chromosome Deletion Chromosomes, Human, Pair 2 (genetics) Female Fibula (abnormalities, diagnostic imaging) Foot Deformities, Congenital (genetics) Gene Expression Regulation, Developmental Humans In Situ Hybridization Infant Infant, Newborn Mice Nuclear Proteins (genetics) Radiography Tibia (abnormalities, diagnostic imaging)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!