Phenotypic variability of a deletion and duplication 6q16.1 → q21 due to a paternal balanced ins(7;6)(p15;q16.1q21).
Constitutional insertional translocations are rare findings in clinical cytogenetics. Here, we report on the unbalanced segregation of a balanced paternal insertional translocation ins(7;6)(p15;q16.1q21) to three children. Investigations by conventional karyotyping, FISH with locus-specific probes, microsatellite marker analysis, and SNP-array based copy number analysis revealed a direct orientation of the inserted segment, a size of 11.3 Mb, and breakpoints between rs4370337 and rs12660854 and rs12110990 and rs4946730 on 6q16.1 and 6q21, respectively, as well as within BAC clone RP11-182J2 on 7p15. A 17-year-old daughter inherited the der(6) chromosome and was affected by severe mental retardation, obesity, and minor anomalies. Two further children inherited the der(7) chromosome. A daughter shows an almost unremarkable phenotype and only minor features in neuropsychological testing at 19 years of age. Her 14-year-old half-brother demonstrates a mild delay in cognitive development most likely jointly caused by the chromosomal rearrangement and asphyxia during delivery. The patient with the deletion confirms the previously reported phenotype of severe mental retardation and obesity in patients with del(6)(q16.2), while both patients with partial trisomy for the same segment of chromosome 6 are further examples for a generally less severe phenotype associated with duplications than with deletions, and even for the recent insight that chromosomal aneusomies of several megabases may go without major clinical consequences.
Division of Human Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
Ana
A
Spreiz
Doris
D
Müller
Sibylle
S
Zotter
Ursula
U
Albrecht
Matthias
M
Baumann
Christine
C
Fauth
Martin
M
Erdel
Johannes
J
Zschocke
Gerd
G
Utermann
Dieter
D
Kotzot
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D058674:Chromosome Duplication / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D016254:Mutagenesis, Insertional / Q000235:genetics*; D009483:Neuropsychological Tests; D010375:Pedigree; D010641:Phenotype; D011247:Pregnancy; D014314:Trisomy / Q000235:genetics; D055815:Young Adult