Link to a recent paper mentioned in an earlier blog. This is the full paper.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?doi=10.1172/JCI29884
This paper represents recent work from researchers / doctors from the UK and USA about the inheritance of Kallmann syndrome and Hypogonadotrophic Hypogonadism.
In the past inheritance was thought due to be a defect in a single gene. This may now not be the case. It appears that the cause may be a combination of gene defects. To date there have been 7 different genes identified that lead to Kallmann syndrome or HH.
While this may not have an effect on the treatment of Kallmann syndrome at the moment but it might lead to a better chance of earlier diagnosis in the future.
Thursday, February 08, 2007
Friday, January 19, 2007
Current views on the genetics of Kallmann Syndrome and
Hypogonadotrophic Hypogonadism.
In the past Kallmann Syndrome (KS) and Hypogonadotrophic Hypogonadism (HH) were thought to be caused by single gene defects.
To date there have been 7 different genes on 7 different chromosomes that have been implicated in causing either or both KS or HH.
It has been recognised that different people with the same detectable gene defect for KS or HH show different symptoms. Even within family groups with the same inherited gene defect there is a variation in symptoms seen.
Recent evidence presented by researchers from Boston, USA (Dr Nelly Pitteloud)and Newcastle, UK (Dr Richard Quinton) has presented a new method to explain the inheritance of KS and HH.
It is proposed that some KS and HH cases are caused by a combination of gene defects on two different genes at the same time. This digenic inheritance of two separate gene defects would help to explain the range of symptoms seen in KS and HH cases. Mild or more severe symptoms would depend on what 2 genes are involved and the type of defect in each of the genes.
This has implications for the prediction of inheritance of KS and HH. On a single gene model it was fairly straight forward to give a 0%, 25%, 50% or 100% chance of passing on a gene defect. With 2 genes involved the situation becomes more complex and it becomes increasingly difficult to predict the chances of passing on KS or HH.
-------------------------------------------------------------------------
The 7 genes currently thought to cause KS or HH:
FGFR-1 (8p 12) Fibronectin growth factor receptor.
NELF (9q 34.3) Nasal embryonic GnRH factor.
KAL-1 (Xp 22.32) Anosmin
PROK2 (3p 21.1) Prokineticin (G protein 73)
PROKR2 (20p 12.3) Prokineticin receptor
GNRHR (4q 21.2) GnRH receptor
GPR54 (19p 13.3) G-protein 54 receptor (also called KISS-2 receptor)
Abstract from a paper due to be published in February's issue of The Journal of Clinical Investigation:
http://www.jci.org/
ENDOCRINOLOGY :
The more mutations the worse the disease in idiopathic hypogonadotropic hypogonadism:
Idiopathic hypogonadotropic hypogonadism (IHH) is an inherited genetic disorder that results in impaired sexual development due to a deficiency in a sex hormone known as GnRH. Although individuals are thought to inherit IHH by having just one gene defect (in any one of a number of genes), not all the evidence supports this hypothesis, for example, not all family members with a given gene defect have the same symptoms.
In a study that appears online on January 18 in advance of publication in the February print issue of the Journal of Clinical Investigation, Nelly Pitteloud and colleagues from Massachusetts General Hospital in Boston show that in two separate families with distinct forms of IHH (Kallmann syndrome and normosmic IHH, respectively) different combinations of several gene defects result in different disease symptoms. In the first family, the individual with the most severe phenotype had mutations in two different genes (FGFR1 and NELF). By contrast, his parents and siblings with only one or other of the mutations exhibited less severe disease. Similarly, in the second family, the most severely affected individual had 2 mutations in her GNRHR genes and 1 mutation in her FGFR1 gene, whereas the less severely affected family members did not have all 3 genetic mutations.
This study indicates that IHH is not caused by a defect in a single gene, something that has implications for the genetic counseling of IHH.
TITLE: Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic hypogonadism
AUTHOR CONTACT:
Nelly Pitteloud
Massachusetts General Hospital, Boston, Massachusetts, USA.
Phone: (617) 724-1830; Fax: (617) 726-5357; E-mail: .
http://www.jci.org/
ENDOCRINOLOGY :
The more mutations the worse the disease in idiopathic hypogonadotropic hypogonadism:
Idiopathic hypogonadotropic hypogonadism (IHH) is an inherited genetic disorder that results in impaired sexual development due to a deficiency in a sex hormone known as GnRH. Although individuals are thought to inherit IHH by having just one gene defect (in any one of a number of genes), not all the evidence supports this hypothesis, for example, not all family members with a given gene defect have the same symptoms.
In a study that appears online on January 18 in advance of publication in the February print issue of the Journal of Clinical Investigation, Nelly Pitteloud and colleagues from Massachusetts General Hospital in Boston show that in two separate families with distinct forms of IHH (Kallmann syndrome and normosmic IHH, respectively) different combinations of several gene defects result in different disease symptoms. In the first family, the individual with the most severe phenotype had mutations in two different genes (FGFR1 and NELF). By contrast, his parents and siblings with only one or other of the mutations exhibited less severe disease. Similarly, in the second family, the most severely affected individual had 2 mutations in her GNRHR genes and 1 mutation in her FGFR1 gene, whereas the less severely affected family members did not have all 3 genetic mutations.
This study indicates that IHH is not caused by a defect in a single gene, something that has implications for the genetic counseling of IHH.
TITLE: Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic hypogonadism
AUTHOR CONTACT:
Nelly Pitteloud
Massachusetts General Hospital, Boston, Massachusetts, USA.
Phone: (617) 724-1830; Fax: (617) 726-5357; E-mail: .
Subscribe to:
Posts (Atom)
