title: Variability in expression of a familial 2.79 Mb microdeletion in chromosome 14q22.1-22.2.
abstract: Deletions in chromosome 14q22-23 have been associated with variable manifestations including malformations of the eye, limbs, palate, and brain, and with developmental and growth delay. Haploinsufficiency of BMP4, OTX2 and possibly SIX6 are thought to contribute to the phenotype. We present a three generation family with four individuals carrying a 2.79 Mb microdeletion 14q22.1-22.2 encompassing BMP4 but not OTX2 nor SIX6. The highly variable manifestations in this family range from multiple congenital malformations with Robin sequence, microphthalmia, postaxial polydactyly, and developmental delay in the index patient to cleft uvula, growth delay, and mild developmental delay in her sister. The adults have a normal intelligence, postaxial polydactyly, and short stature or early cataract. Genotype-phenotype correlations suggest that the severity of eye manifestations in 14q22 deletions are influenced by the size of the deletion, but the marked intrafamilial variability observed in this family, as well as in familial BMP4 or OTX2 intragenic mutations points to additional modifiers outside this region.
authors.affiliation: Center for Human Genetics, University Hospital Leuven, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Aimé
authors.initials: A
authors.lastname: Lumaka
authors.forename: Christine
authors.initials: C
authors.lastname: Van Hole
authors.forename: Ingele
authors.initials: I
authors.lastname: Casteels
authors.forename: Els
authors.initials: E
authors.lastname: Ortibus
authors.forename: Veerle
authors.initials: V
authors.lastname: De Wolf
authors.forename: Joris R
authors.initials: JR
authors.lastname: Vermeesch
authors.forename: Tshilobo
authors.initials: T
authors.lastname: Lukusa
authors.forename: Koen
authors.initials: K
authors.lastname: Devriendt
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics; D000328:Adult; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D055028:Comparative Genomic Hybridization; D005190:Family; D005260:Female; D015870:Gene Expression; D023061:Gene Order; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
chemical_list: D055415:Bone Morphogenetic Protein 4