title: A pure familial 6q15q21 split duplication associated with obesity and transmitted with partial reduction.
abstract: Familial transmission of chromosome 6 duplications is rare. We report on the first observation of a maternally-inherited pure segmental 6q duplication split into two segments, 6q15q16.3 and 6q16.3q21, and associated with obesity. Obesity has previously been correlated to chromosome 6 q-arm deletion but has not yet been assessed in duplications. The aim of this study was to characterize the structure of these intrachromosomal insertional translocations by classic cytogenetic banding, array-CGH, FISH, M-banding and genotyping using microsatellites and SNP array analysis, in a mother and four offspring. The duplicated 6q segments, 9.75 Mb (dup 1) and 7.05 Mb (dup 2) in size in the mother, were inserted distally into two distinct chromosome 6q regions. They were transmitted to four offspring. A son and a daughter inherited the two unbalanced insertions and displayed, like the mother, an abnormal phenotype with facial dysmorphism, intellectual disability, and morbid obesity. Curiously, two daughters with a normal phenotype inherited only the smaller segment, 6q16.3q21. The abnormal phenotype was associated with the larger proximal 6q15q16.3 duplication. We hypothesize a mechanism for this exceptional phenomenon of recurrent reduction and transmission of the duplication during meiosis in a family. We expect the interpretation of our findings to be useful for genetic counseling and for understanding the mechanisms underlying these large segmental 6q duplications and their evolution.
authors.affiliation: CHU-Reims, HMB, Service de Génétique, France.|CHU-Reims, HMB, Plateforme Régionale de Biologie Innovante, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Landais
authors.affiliation: CHU-Reims, HMB, Service de Génétique, France.|Université de Reims Champagne-Ardenne, UFR de médecine, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Leroy
authors.affiliation: Laboratoire de Génétique, Pasteur Cerba, Cergy Pontoise, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Kleinfinger
authors.affiliation: CHU-Reims, HMB, Service de Génétique, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Brunet
authors.affiliation: Service de génétique Médicale, Laboratoire de génétique moléculaire, CHU Hopital Necker enfants malades, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Koubi
authors.affiliation: CHU-Reims, American Memorial Hospital, Service de Pédiatrie A, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Pietrement
authors.affiliation: Université de Reims Champagne-Ardenne, UFR de médecine, France.|CHU-Reims, American Memorial Hospital, Service de Chirurgie pédiatrique, France.
authors.forename: Marie-Laurence
authors.initials: ML
authors.lastname: Poli-Mérol
authors.affiliation: CHU-Reims, American Memorial Hospital, Service de Chirurgie pédiatrique, France.|SFR CAP Santé, Reims, EA 3801, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Fiquet
authors.affiliation: CHU-Reims, American Memorial Hospital, Service de Pédiatrie A, France.
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Souchon
authors.affiliation: CHU-Nancy, Laboratoire de Génétique Médicale, Nancy Université, France.
authors.forename: Mylène
authors.initials: M
authors.lastname: Beri
authors.affiliation: CHU-Nancy, Laboratoire de Génétique Médicale, Nancy Université, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Jonveaux
authors.affiliation: CHU-Reims, Laboratoire de Biochimie Médicale et Biologie Moléculaire, CNRS UMR 6198, UFR, Médecine, France.
authors.forename: Roselyne
authors.initials: R
authors.lastname: Garnotel
authors.affiliation: CHU-Reims, HMB, Service de Génétique, France.|Université de Reims Champagne-Ardenne, UFR de médecine, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Gaillard
authors.affiliation: CHU-Reims, HMB, Service de Génétique, France.|SFR CAP Santé, Reims, EA 3801, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Doco-Fenzy
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002871:Chromosome Banding; D002896:Chromosomes, Human, Pair 6; D055028:Comparative Genomic Hybridization; D005190:Family; D005260:Female; D005817:Genetic Counseling; D018740:Genetic Heterogeneity; D006801:Humans; D040582:Inheritance Patterns; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D008297:Male; D008540:Meiosis; D018895:Microsatellite Repeats; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D009765:Obesity / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D010641:Phenotype; D014314:Trisomy
keywords: Array-Based Comparative Genomic Hybridization; SNP array; chromosome 6; chromosome segregation; duplication 6q15q21; intellectual disability; obesity