title: Multiple genomic aberrations in a patient with mental retardation and hypogonadism: 45,X/46,X,psu dic(Y) karyotype, thyroid hormone receptor beta (THRB) mutation and heterozygosity for Wilson disease.
abstract: We report on multiple genomic aberrations in a patient with mental retardation. In addition, he had hypogonadism, elevated thyroid hormone levels, hearing loss, delayed speech development and mild dysmorphic features. First, we identified a mosaic karyotype, 45,X/46,X,psu dic(Y). The pseudo-dicentric Y chromosome has three short arm segments. Second, we found a germline mutation (Pro453Thr) of the thyroid hormone receptor beta (THRB) which is associated with resistance to thyroid hormone. Third, he was found to be a carrier of a heterozygous ATP7B mutation (c.2575 + 5G > C), the Wilson disease gene. Even though an array-CGH (with a density of approximately 1 Mb) did not reveal any further genomic gains or losses, we cannot exclude that all contributing factors have been identified. However, this case report shows that with increasing technological possibilities we can find more than one cause for developmental problems in a single patient. The identification of multiple causes in a single patient may complicate explaining the disorder and genetic counseling.
authors.affiliation: Center for Clinical and Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. f.j.hes@lumc.nl
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: Hes
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Madan
authors.forename: I Shan
authors.initials: IS
authors.lastname: Rombout-Liem
authors.forename: Karoly
authors.initials: K
authors.lastname: Szuhai
authors.forename: Helena
authors.initials: H
authors.lastname: Sørensen
authors.forename: Hans Kristian Ploos
authors.initials: HK
authors.lastname: van Amstel
authors.forename: Egbert
authors.initials: E
authors.lastname: Bakker
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
authors.forename: Johannes W
authors.initials: JW
authors.lastname: Smit
authors.forename: Kerstin
authors.initials: K
authors.lastname: Hansson
mesh_terms: D002869:Chromosome Aberrations; D041322:Chromosomes, Human, Y; D006060:Gonadal Dysgenesis, Mixed / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D006527:Hepatolenticular Degeneration / Q000150:complications / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007006:Hypogonadism / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics*; D007621:Karyotyping; D008297:Male; D009030:Mosaicism; D009154:Mutation; D037042:Thyroid Hormone Receptors beta / Q000235:genetics*; D055815:Young Adult
chemical_list: D037042:Thyroid Hormone Receptors beta