title: Inherited mosaicism for the supernumerary marker chromosome in cat eye syndrome: inter- and intra-individual variation and correlation to the phenotype.
abstract: We have studied a family with repeated transmission of mosaicism for a supernumerary marker chromosome (SMC), giving rise to varying symptoms of the cat eye syndrome (CES) in the offspring. The frequency of the SMC was investigated using FISH with probes from the CES critical region on lymphocytes as well as buccal cells. The same probes were used to study the frequency of the SMC in spermatozoa from the father. The SMC was characterized in detail using array-CGH and was found to correspond to a symmetrical cat eye SMC type I, with two extra copies of the most proximal part of 22q11, not extending into the classical 22q11.2 deletion region. Mosaicism for the SMC was detected in 4 out of 7 family members, the father and all his three children. The degree of mosaicism varied greatly between individuals as well as between tissues, with twice as many cells with the SMC in epithelial cells compared to blood. The highest frequency (almost 50%) was found in spermatozoa from the father. There was a direct correlation between the degree of mosaicism and the symptoms, varying from no obvious symptoms to classical CES. The study confirms the occurrence of direct transmission of SMC-mosaicism in CES. The results indicate that examination of parental epithelial cells should be preferred compared to blood cells in order to exclude a recurrence risk in parents of a child with CES. Interphase FISH analysis of spermatozoa is the most sensitive method to exclude paternal germ line mosaicsm.
authors.affiliation: Clinical Genetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden. malin.kvarnung@karolinska.se
authors.forename: Malin
authors.initials: M
authors.lastname: Kvarnung
authors.forename: Anna
authors.initials: A
authors.lastname: Lindstrand
authors.forename: Helena
authors.initials: H
authors.lastname: Malmgren
authors.forename: Anders
authors.initials: A
authors.lastname: Thåström
authors.forename: Lena
authors.initials: L
authors.lastname: Jacobson
authors.forename: Niklas
authors.initials: N
authors.lastname: Dahl
authors.forename: Johanna
authors.initials: J
authors.lastname: Lundin
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Blennow
mesh_terms: D000782:Aneuploidy; D002648:Child; D025063:Chromosome Disorders / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D005124:Eye Abnormalities; D005190:Family; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009030:Mosaicism; D010641:Phenotype; D013094:Spermatozoa
chemical_list: D005819:Genetic Markers