The DHH gene provides instructions for making a member of the hedgehog protein family. Hedgehog proteins are important for early development in many parts of the body. The protein produced from the DHH gene is believed to be involved in male-typical sex development and in the formation of the perineurium, the protective membrane around each bundle of fibers within a nerve.
Health Conditions Related to Genetic Changes
DHH gene variants (also called mutations) have been identified in a small number of people with Swyer syndrome, also known as 46,XY complete gonadal dysgenesis or 46,XY pure gonadal dysgenesis. Swyer syndrome is a condition that affects sex development. Affected individuals have two altered copies of the DHH gene in each cell.
Sex development usually follows a particular pattern based on an individual's chromosomes. People usually have 46 chromosomes in each cell. Two of the 46 chromosomes, known as X and Y, are called sex chromosomes because they help determine whether a person will develop male or female sex characteristics. Girls and women typically have two X chromosomes (46,XX karyotype), and boys and men typically have one X chromosome and one Y chromosome (46,XY karyotype). However, individuals with Swyer syndrome have a male-typical chromosome pattern (46,XY karyotype), but they develop female-typical sex characteristics.
Variants in the DHH gene in people with Swyer syndrome affect the process of sex development, preventing affected individuals with a 46,XY karyotype from developing male gonads (testes) and causing them to develop female reproductive structures (a uterus and fallopian tubes).More About This Health Condition
DHH gene variants have been identified in people with 46,XY disorder of sex development, also known as partial gonadal dysgenesis. These individuals have one altered DHH gene in each cell. They may have external genitalia that do not look clearly male or clearly female (ambiguous genitalia) or other changes in the genitals and reproductive organs.
Some people with the features of 46,XY disorder of sex development caused by DHH gene variants also have nerve abnormalities. This combination of features is a condition called 46,XY gonadal dysgenesis with minifascicular neuropathy. The nerve abnormalities affect nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound (the peripheral nervous system). Affected individuals may experience weakness and loss of sensation in their extremities (peripheral neuropathy).
Other Names for This Gene
- desert hedgehog homolog (Drosophila)
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Canto P, Söderlund D, Reyes E, Méndez JP. Mutations in the desert hedgehog (DHH) gene in patients with 46,XY complete pure gonadal dysgenesis. J Clin Endocrinol Metab. 2004 Sep;89(9):4480-3. Erratum in: J Clin Endocrinol Metab. 2004 Nov;89(11):5453. Citation on PubMed
- Canto P, Vilchis F, Söderlund D, Reyes E, Méndez JP. A heterozygous mutation in the desert hedgehog gene in patients with mixed gonadal dysgenesis. Mol Hum Reprod. 2005 Nov;11(11):833-6. Epub 2006 Jan 3. Citation on PubMed
- Das DK, Sanghavi D, Gawde H, Idicula-Thomas S, Vasudevan L. Novel homozygous mutations in Desert hedgehog gene in patients with 46,XY complete gonadal dysgenesis and prediction of its structural and functional implications by computational methods. Eur J Med Genet. 2011 Nov-Dec;54(6):e529-34. doi: 10.1016/j.ejmg.2011.04.010. Epub 2011 Jul 23. Citation on PubMed
- King TF, Conway GS. Swyer syndrome. Curr Opin Endocrinol Diabetes Obes. 2014 Dec;21(6):504-10. doi: 10.1097/MED.0000000000000113. Review. Citation on PubMed
- Mohnach L, Fechner PY, Keegan CE. Nonsyndromic Disorders of Testicular Development. 2008 May 21 [updated 2016 Jun 2]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from http://www.ncbi.nlm.nih.gov/books/NBK1547/ Citation on PubMed
- Sugie K, Futamura N, Suzumura A, Tate G, Umehara F. Hereditary motor and sensory neuropathy with minifascicle formation in a patient with 46XY pure gonadal dysgenesis: a new clinical entity. Ann Neurol. 2002 Mar;51(3):385-8. Citation on PubMed
- Umehara F, Tate G, Itoh K, Osame M. Minifascicular neuropathy: a new concept of the human disease caused by desert hedgehog gene mutation. Cell Mol Biol (Noisy-le-grand). 2002 Mar;48(2):187-9. Review. Citation on PubMed