title: An interstitial, apparently-balanced chromosomal insertion in the etiology of Langer-Giedion syndrome in an Asian family.
abstract: Langer-Giedion syndrome (LGS; MIM 150230), also called trichorhinophalangeal syndrome type II (TRPS2), is a contiguous gene syndrome caused by a one-copy deletion in the chromosome 8q23-q24 region, spanning the genes TRPS1 and EXT1. We identified an LGS family with two affected and two unaffected siblings from unaffected parents. To investigate the etiology of recurrence of LGS in this family, array CGH was performed on all family members. We identified a 7.29 Mb interstitial deletion at chromosome region 8q23-q24 in the two affected siblings, but no such deletion in the unaffected family members. However, the mother and one of the two unaffected siblings carried a 1.29 Mb deletion at chromosome region 8q24.1, sharing the distal breakpoint with the larger deleted segment found in the affected siblings. Another unaffected sibling had a 6.0 Mb duplication, sharing the proximal breakpoint of the deletion in the affected siblings. Karyotypic and FISH analyses in the unaffected mother revealed an insertional translocation of 8q23-q24 genomic material into chromosome 13: 46,XX,ins(13;8)(q33;q23q24). This insertional translocation in the mother results in the recurrence of LGS in this family, highlighting the importance of submicroscopic rearrangements in the genetic counseling for LGS.
authors.affiliation: Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 110-799, Republic of Korea.
authors.forename: Byung-Joo
authors.initials: BJ
authors.lastname: Min
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Ko
authors.forename: Myung-Eui
authors.initials: ME
authors.lastname: Seo
authors.forename: Jin-Sun
authors.initials: JS
authors.lastname: Choi
authors.forename: Sun Kyung
authors.initials: SK
authors.lastname: Oh
authors.forename: Jane
authors.initials: J
authors.lastname: Jeon
authors.forename: Eunhyun
authors.initials: E
authors.lastname: Kim
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Moon
authors.forename: In Ho
authors.initials: IH
authors.lastname: Choi
authors.forename: Charles
authors.initials: C
authors.lastname: Lee
authors.forename: Ok-Hwa
authors.initials: OH
authors.lastname: Kim
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Cho
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
mesh_terms: D059786:Abnormal Karyotype; D000293:Adolescent; D001483:Base Sequence; D019457:Chromosome Breakage; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D015826:Langer-Giedion Syndrome / Q000000981:diagnostic imaging / Q000235:genetics*; D008297:Male; D016254:Mutagenesis, Insertional; D020641:Polymorphism, Single Nucleotide; D011859:Radiography; D017384:Sequence Deletion; D055815:Young Adult
keywords: Array comparative genome hybridization (aCGH); Fluorescent in situ hybridization (FISH); Interstitial chromosomal insertion; Langer–Giedion syndrome (LGS)