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 amosaic 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 ∼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.

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doi.org/10.1002/ajmg.a.33004, hdl.handle.net/1765/24056
American Journal of Medical Genetics. Part A
Erasmus MC: University Medical Center Rotterdam

Hes, F., Madan, K., Rombout-Liem, S., Szuhai, K., Sørensen, H., van Amstel, H. K. P., … Hansson, K. (2009). 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. American Journal of Medical Genetics. Part A, 149(10), 2231–2235. doi:10.1002/ajmg.a.33004