Genetic Endocrinology

Endocrinology deals with hormones and the many ways in which they can affect health and disease in humans. In many endocrine conditions the underlying genetic abnormalities are not understood. We study the genetics, genomics and transcriptomics of endocrine conditions. Epigenetic alterations of the genome are also likely to be involved in several endocrine conditions.

Claus Højbjerg Gravholt at Google Scholar

Sex Chromosome Abnormalities

Sex chromosomes are essential for our understanding of sex. Normally, if we have two X chromosomes (46,XX), we  develop into females, and if we have an X and a Y chromosome (46,XY), we become males. However, in a number of conditions things are not that straight forward.
Turner syndrome (45,X), where one misses an X chromosome and has a female phenotype, is associated with infertility, hypogonadism, short stature, type 2 diabetes, autoimmune disease and other conditions.
Klinefelter syndrome (47,XXY), where an extra X chromosome  and a male phenotype are present, is associated with infertility, hypogonadism, tall stature, type 2 diabetes, autoimmune disease and other conditions.
Females with 46,XY disorder of sex development (DSD) and males with 46,XX DSD and other conditions with DSD are also observed.

The X and Y chromosome with depictions of the pesudoautosomal region 1 and 2. From Endocr Rev, bnac016,

Congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH) is an autosomal recessive inherited disease. It is the most common genetic endocrine disorder. In CAH cortisol synthesis is aberrant due to the defect of 21 hydroxylase enzyme or other enzymes. About 95 % of the mutations occur in the 21-hydroxylase gene, but a number of other genes are also involved. Currently, we have much knowledge about this condition during childhood, while considerably less is known about the development during adult life. However, data from Sweden suggest an increased morbidity due to a range of diseases likely linked to the treatment of CAH and the underlying genetic condition.

Incidence of congenital adrenal hyperplasia during 1943-2018.

Aim of research

Our research is aimed at elucidating the genetics, genomics and epigenetics of endocrine diseases broadly and more specifically of conditions such as Turner syndrome, Klinefelter syndrome, 46,XX DSD, 46,XY DSD, and CAH. We link such data with epidemiological and clinical data and aim to elucidate new candidate genes, as well as new clinical biomarkers.

The complex genetics underlying Turner syndrome. From Endocrine Reviews, bnac016,

Current research activities

  • X chromosome inactivation, epigenetics and the transcriptome
  • Congenital adrenal hyperplasia – epidemiology, genetics, screening and clinical features: a nationwide study
  • The origin, genotype and phenotype of sex chromosome syndromes
  • Integrative analysis of epigenomic and transcriptomic data in Turner syndrome
  • The genetic background for the neuropsychologic phenotype in Klinefelter Syndrome
  • The ovary and the testis in Turner and Klinefelter syndrome – what causes infertility and hypogonadism
  • The cardiovascular phenotype in     Turner syndrome – links to the genotype

group leader

Claus Højbjerg Gravholt

Professor, MD, PhD, consultant (Endocrinology), Group leader