title: Small reciprocal insertion detected by spectral karyotyping (SKY) and delimited by array-CGH analysis.
abstract: A 5.4-year-old male propositus is reported with mild dysmorphic features including hypoplasia of the radial part of both hands affecting thenar, thumb and fingers 2-3, incomplete syndactyly of fingers 3-4, single palmar creases, brachymesophalangia of toes 3-5, dissociated retardation of bone age, telecanthus, spina bifida occulta, cryptorchidism, muscular hypotonia, and borderline mental retardation. His karyotype was unbalanced, 46,XY,der(16)ins(4;16)(q26q28.1; q12.1q12.2)pat. In the propositus' father who had brachydactyly of fingers 2-5 and brachymesophalangia of toes 3-5 the insertion was reciprocal, 46,XY,rep ins(4;16)(q26q28.1;q12.1q12.2). Insertions are rare, reciprocal insertions most unusual. The characterization of the insertion in the propositus and the detection of its reciprocity in the father were achieved by the application of spectral karyotyping (SKY). Further examination of the propositus' unbalanced genome by array-CGH analysis delimited the chromosomal locations of the deletion/insertion rearrangement on a 0.5-2 Mb resolution level and allowed to design specific BAC FISH analyses that pinpointed the borders of the affected segments. The rearrangement involved a segment of 7.7 Mb between RP11-1030 g22 and RP11-52k8 at the chromosomal regions 4q26 and 4q28.1, respectively, and a segment of 2.8 Mb between RP11-242n20 at 16q12.1 and RP11-324d17 at 16q12.2. A simple molecular genetic explanation of the phenotype cannot be given. A relation to the Townes Brocks gene (SALL1) located 340 kb proximal of the 16q12 deletion/insertion is unlikely. Possibly more relevant is an overlap of the 16q12 deletion/insertion with a small deletion of the syntenic chromosomal region in the mouse that causes a developmental disorder of digits ("Fused toes").
authors.affiliation: Department of Clinical Genetics, University Medical Center Carl Gustav Carus, Fetscherstr. 74, D-01307 Dresden, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Matthaei
authors.forename: Walter
authors.initials: W
authors.lastname: Werner
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Gerlach
authors.forename: Ulrike
authors.initials: U
authors.lastname: Koerner
authors.forename: Sigrid
authors.initials: S
authors.lastname: Tinschert
authors.forename: Inna
authors.initials: I
authors.lastname: Nitz
authors.forename: Alexander
authors.initials: A
authors.lastname: Herr
authors.forename: Andreas
authors.initials: A
authors.lastname: Rump
authors.forename: Oliver
authors.initials: O
authors.lastname: Bartsch
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Hinkel
authors.forename: Evelin
authors.initials: E
authors.lastname: Schrock
authors.forename: Konrad
authors.initials: K
authors.lastname: Oexle
mesh_terms: D002648:Child; D002675:Child, Preschool; D022202:Chromosomes, Artificial, Bacterial; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D017880:Limb Deformities, Congenital / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D032681:Spectral Karyotyping; D014178:Translocation, Genetic