[Marc]

This is a letter that was sent to my doctors from an endocrinologist I was seeing a few years back.

You will remember that a few weeks ago, I reported our Clinical Research Center test results, which indicated that Marc had idiopathic partial hypogonadotrophic hypogonadism.
An important piece of new information has been accrued since I wrote that report, however. I have belatedly received the full Genetics Laboratory report from Dr. Paul W.K. Wong's Genetics Laboratory at Rush-Presbyterian St Luke's Medical Center and discussed their findings with him.
They examined 45 blood cells for chromosomes and karyotyped seven of the cells. Forty-three of the cells(95.5%) contained a normal male 46, XY karyotype, and the remaining two cells(4.5%) showed a 46, XX normal female karyotype. They recommended cytogenetic analysis of the skin biopsy sample to confirm this finding. Let me make you aware, however, that while this set of findings is disturbing, it is not definitive, because the threshold for significant mosaicism(as opposed to laboratory artifact) is a 5% representation of a second cell line. However, having said that, the fact that the two atypical cells both have the same karyotype make it suspicious that there may well be an extremely low level of mosaicism or chimerism.
I subsequently framed an anonymous genetics question about this to Dr Darrel Waggoner, Director of medical Genetics here. While he stated that chromosomal abnormalities are easier to find in skin cells than blood cells, because of the survival disadvantage of abnormal cells over time, the fact that the minor apparent cell lines were not abnormal, makes it unlikely that the skin biopsy will be helpful in this case.
It is unclear how a minor cell line with normal 46, XX chromosome complement could explain hypothalamic hypogonadotrophic hypogonadism, unless these cells are both disproportionally expressed in the hypothalamus and carry the mutant KAL gene for hypogonadotrophic hypogonadism.