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Study identifies pathway required for normal reproductive development
Date:10/15/2007

involvement in these systems led the researchers to investigate the proteins potential role in GnRH deficiency in human and mice.

The MGH team analyzed the PROK2 genes of 100 study participants: 50 with Kallmann syndrome and 50 with IHH and a normal sense of smell. Three members from the same family in Portugal two brothers and a sister had identical defects in both copies of the PROK2 gene. Further study of this family revealed another brother with the mutation in only one PROK2 copy and a normal reproductive history. Five siblings of these individuals now in their 70s had died in infancy; similar early deaths have been seen in the PROK2-deficient mice. Interestingly, while the two affected brothers both had Kallmann syndrome, their affected sister had a normal sense of smell but did not experience normal puberty.

Until recently, IHH with a normal sense of smell and Kallmann syndrome with no sense of smell had been considered two distinct clinical entities, says Pitteloud, an assistant professor of Medicine at Harvard Medical School. We now have described several kindreds in which different family members exhibit both syndromes yet harbor the identical mutation. So, it looks like additional gene defects or environmental cues modify how these syndromes develop in affected families.

The collaborative UC Irvine team was led by Qun-Yong Zhou, PhD, a professor of Pharmacology in its School of Medicine. His group has made fundamental contributions to the understanding of the neurobiological functions of prokineticin and its receptors. Their analysis of the reproductive status of mice lacking functional copies of Prok2 gene revealed that the animals reproductive defect is due to the abnormal migration of neurons that secrete GnRH.

Many recessive human genetic disorders, particularly the ones that have associated infertility symptom, are very difficult or almost infeasible to investigate using genetic analysis. The curr
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
Source:Eurekalert

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