A girl with neurofibromatosis type 1, atypical autism and mosaic ring chromosome 17

• Published in: American journal of medical genetics. Part A Vol. 143A; no. 1; pp. 76 - 81
• Main Authors: Havlovicova, Marketa, Novotna, Drahuse, Kocarek, Eduard, Novotna, Kamila, Bendova, Sarka, Petrak, Borivoj, Hrdlicka, Michal, Sedlacek, Zdenek
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-01-2007; Wiley-Liss
• Subjects: Adult and adolescent clinical studies; autism; Autistic Disorder - complications; Autistic Disorder - diagnosis; Autistic Disorder - genetics; Biological and medical sciences; cancer susceptibility; Child; Child clinical studies; Chromosomes, Human, Pair 17 - genetics; Developmental disorders; Female; Humans; In Situ Hybridization, Fluorescence; Infantile autism; Intellectual deficiency; Medical genetics; Medical sciences; mental retardation; Mosaicism; neurofibromatosis; Neurofibromatosis 1 - complications; Neurofibromatosis 1 - diagnosis; Neurofibromatosis 1 - genetics; Neurology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; ring chromosome 17; Ring Chromosomes; ring syndrome; Tumors of the nervous system. Phacomatoses; Chromosomal aberration; Skin disease; Pathogenesis; Developmental disorder; Mental retardation; Genetic determinism; Neurofibromatosis Recklinghausen; Predisposition; ring syndrome; Female; neurofibromatosis; Benign neoplasm; Neurological disorder; Child; Human; Nervous system diseases; cancer susceptibility; Phacomatosis; Malignant tumor; Syndrome; Genetic disease; Autism; Sensitivity; Ring chromosome; Chromosome E17; Intellectual deficiency; Abnormal chromosome; Mosaicism; Atypical; ring chromosome 17; Cancer
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.31569

We describe a girl with neurofibromatosis type 1 (NF1), mild dysmorphic features, growth and mental retardation, autism, and mosaicism of ring chromosome 17 and chromosome 17 monosomy. The extent of genetic material deleted from the ring chromosome was determined using a combination of classical cytogenetics, fluorescence in situ hybridization (FISH) and multiplex ligation‐dependent probe amplification (MLPA) to be 0.6–2.5 Mb on 17p, and up to about 10 Mb on 17q. Based on our observations and on a review of the literature we argue that in addition to a universal “ring syndrome” which is based on ring instability and is less specific for the chromosome involved, various ring chromosomes underlie their own characteristic phenotypes. We propose that the symptoms leading to the diagnosis of NF1 in our patient could be attributed to mosaic hemizygosity for the NF1 gene in some of her somatic cells. A similar mechanism or a direct involvement of respective disease genes in the aberration could possibly influence also the development of autism and other symptoms. We raise a question if the loss of one copy of chromosome 17 from a substantial fraction of somatic cells can have specific consequences also for future risks of the patient, for example, due to the mosaic hemizygosity for the BRCA1 and TP53 genes. © 2006 Wiley‐Liss, Inc.