title: 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.
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.
authors.affiliation: Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, Netherlands. M.Poot@umcutrecht.nl
authors.forename: Martin
authors.initials: M
authors.lastname: Poot
authors.forename: Ruben
authors.initials: R
authors.lastname: van't Slot
authors.forename: Romina
authors.initials: R
authors.lastname: Leupert
authors.forename: Vera
authors.initials: V
authors.lastname: Beyer
authors.forename: Eberhard
authors.initials: E
authors.lastname: Passarge
authors.forename: Thomas
authors.initials: T
authors.lastname: Haaf
mesh_terms: D000328:Adult; D001921:Brain / Q000254:growth & development; D015816:Cell Adhesion Molecules, Neuronal; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D020732:Cytogenetic Analysis / Q000379:methods; D005145:Face / Q000503:physiopathology; D005192:Family Health; D005260:Female; D006801:Humans; D043884:Receptor, Cannabinoid, CB1; D020886:Somatosensory Disorders / Q000235:genetics*; D013064:Speech Disorders / Q000235:genetics*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D043884:Receptor, Cannabinoid, CB1