A father and son with mental retardation, a characteristic face, inv(12), and insertion trisomy 12p12.3-p11.2

• Published in: American journal of medical genetics. Part A Vol. 140A; no. 3; pp. 238 - 244
• Main Authors: Liang, Desheng, Wu, Lingqian, Pan, Qian, Harada, Naoki, Long, Zhigao, Xia, Kun, Yoshiura, Koh-ichiro, Dai, Heping, Niikawa, Norio, Cai, Fang, Xia, Jiahui
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.02.2006; Wiley-Liss
• Subjects: Abnormalities, Multiple - genetics; Abnormalities, Multiple - pathology; Adult; Adult and adolescent clinical studies; Biological and medical sciences; Chromosome aberrations; Chromosome Banding; Chromosome Breakage - genetics; Chromosome Inversion; Chromosomes, Artificial, Bacterial - genetics; Chromosomes, Human, Pair 12 - genetics; Contig Mapping; duplication; Face - abnormalities; Fathers; FISH; genome-wide copy number detection; Humans; In Situ Hybridization, Fluorescence; Infant; Intellectual deficiency; Intellectual Disability - pathology; inversion; Karyotyping; Male; Medical genetics; Medical sciences; mental retardation; Models, Genetic; Nuclear Family; partial trisomy 12p; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Trisomy; Chromosomal aberration; Partial trisomy; Copy number; Insertion; Inversion; Developmental disorder; Chromosome C12; Mental retardation; duplication; genome-wide copy number detection; partial trisomy 12p; Fluorescence in situ hybridization; Intellectual deficiency; FISH; Abnormal chromosome; Mutation; Chromosome duplication; Detection; Face; Genome; Father
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.31077

A male patient with mental retardation (MR) and mild facial features was shown by high‐resolution G‐banding to have pericentric inversion of chromosome 12 with an unknown segment inserted into the long arm of the inverted chromosome [46,XY,inv(12)(pter → p11.2::q14.1 → p11.2::?::q14.1 → qter)]. Both the inverted chromosome 12 and clinical manifestations were transmitted to his son. Karyotypes of the propositus' parents were normal. Studies with fluorescence in situ hybridization (FISH) in both the propositus and his son revealed that the extra segment was derived from 12p. Further FISH mapping and the genome‐wide copy number detection by GeneChip Mapping 100K Array showed that an 11‐Mb segment of 12p between two BAC clones, RP11‐22H10 and RP11‐977P2, was inserted at one of the reunion points in the long arm of the inv(12) chromosome. Analysis of parent–child transmissions of duplicated alleles using microsatellite markers defined the maternal origin of the chromosomal anomaly in the propositus and suggested a mechanism of its formation through a sister‐chromatid rearrangement (SCR), that is, mismatched pairing and unequal crossover between sister chromatids as well as three break rearrangements including a U type rearrangement. Karyotypes of the propositus and his son were thus inv(12)(pter → p11.22::q14.1 → p12.3::q14.1 → qter). This is the first report of “pure” proximal 12p‐trisomy including p12.3–p11.22 region. © 2006 Wiley‐Liss, Inc.