Three de novo losses and one insertion within a pericentric inversion of chromosome 6 in a patient with complete absence of expressive speech and reduced pain perception

• Published in: European journal of medical genetics Vol. 52; no. 1; pp. 27 - 30
• Main Authors: Poot, Martin, van't Slot, Ruben, Leupert, Romina, Beyer, Vera, Passarge, Eberhard, Haaf, Thomas
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Masson SAS 01-01-2009; Elsevier
• Subjects: Adult; Biological and medical sciences; Brain - growth & development; Cell Adhesion Molecules, Neuronal; Chromosome Aberrations; Chromosome Mapping; Chromosomes, Human, Pair 6; CNR1 gene; Cytogenetic Analysis - methods; De novo loss; Deletion; Face - physiopathology; Family Health; Female; FISH; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genetics of eukaryotes. Biological and molecular evolution; Humans; Insertion; Inversion; Medical Education; Medical genetics; Medical sciences; Receptor, Cannabinoid, CB1; SNP array; Somatosensory Disorders - genetics; Speech Disorders - genetics; Deletion; Insertion; FISH; Inversion; De novo loss; SNP array; CNR1 gene; Chromosomal aberration; Human; Loss; Chromosome 6; Patient; Chromosome C6; De novo; Pain; Gene; Fluorescence in situ hybridization; Pericentric inversion; Abnormal chromosome; Genetics; Speech; Perception; Single nucleotide polymorphism
• ISSN: 1769-7212; 1878-0849
• DOI: 10.1016/j.ejmg.2008.11.002

Abstract A 32-year-old female patient, observed for 30 years because of a distinctive phenotype consisting of a dysmorphic face non-progressive deficit of motor control, lack of speech development, reduced sensitivity to pain, with a known, complex interstitial deletion 6q14 within a de novo pericentric inversion 6p11.2;q15, was re-examined at the molecular level. Applying the Infinium HumanHap300 BeadChip array and BAC-based FISH we found two new non-contiguous microdeletions in addition to the one detected previously by high resolution G-band analysis. A 360 kb loss in band 6p12.3, containing the genes RHAG , CRISP1 , 2 , and 3 , and PGK2 , a 1.15 Mb loss in 6p12.2-p12.1, containing the genes PKHD1 , IL17 , MCM3 , EFHC1 , and TRAM2 genes, and an 11.9 Mb loss in region 6q14.3-q16.1, reported previously, were mapped on the rearranged chromosome 6. The latter loss contained the central cannabinoid receptor isoform b ( CNR1 ), which may be involved in brain development and function. Since the maternal SNPs were retained this rearrangement of chromosome 6 is most likely of paternal origin.