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

Am J Med Genet A. 2009 Oct;149A(10):2231-5. doi: 10.1002/ajmg.a.33004.

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.

Publication types

  • Case Reports

MeSH terms

  • Chromosome Aberrations
  • Chromosomes, Human, Y
  • Gonadal Dysgenesis, Mixed / complications
  • Gonadal Dysgenesis, Mixed / diagnosis
  • Gonadal Dysgenesis, Mixed / genetics*
  • Hepatolenticular Degeneration / complications
  • Hepatolenticular Degeneration / genetics*
  • Heterozygote
  • Humans
  • Hypogonadism / complications
  • Hypogonadism / diagnosis
  • Hypogonadism / genetics*
  • Intellectual Disability / complications
  • Intellectual Disability / genetics*
  • Karyotyping
  • Male
  • Mosaicism
  • Mutation
  • Thyroid Hormone Receptors beta / genetics*
  • Young Adult

Substances

  • Thyroid Hormone Receptors beta