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.
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.
Hes
Frederik J
FJ
Center for Clinical and Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. f.j.hes@lumc.nl
Madan
Kamlesh
K
Rombout-Liem
I Shan
IS
Szuhai
Karoly
K
Sørensen
Helena
H
van Amstel
Hans Kristian Ploos
HK
Bakker
Egbert
E
Visser
Theo J
TJ
Smit
Johannes W
JW
Hansson
Kerstin
K
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
D037042:Thyroid Hormone Receptors beta