last update: 06/06/2006

Background to disease

OMIM 30940

Menkes disease is a disorder of copper metabolism. Clinical features include abnormal hair, abnormal faces, depigmentation, hypothermia, arterial degeneration, osteoporosis and neurodegeneration especially in the cerebellum. Death usually occurs before two years of age.

Menkes disease is inherited in an X-linked recessive pattern, incidence is approximately 1 in 300000 live births. The Menkes gene is located at Xq13 and encodes a Cu(2+)-transporting ATPase, alpha polypeptide (OMIM 300011). It contains 23 exons encoding a 1500 amino acid residue and covers 140kb.

In those Menkes patients in whom a mutation has been identified, the mutation is unique, suggesting an independent origin for the mutation in most patients, as expected for a reproductive lethal X-linked disorder. Deletions of varying sizes within the gene have been identified in 15 – 25% of patients. Other types of mutations identified include duplication, splice site, missence and nonsense. Splice site mutations which reduce but do not abolish normal mRNA production are specifically associated with occipital horn syndrome and mild Menkes phenotypes.

Two intragenic, highly polymorphic CA repeats have been identified, making linkage analysis a viable alternative to direct mutation analysis.

Laboratory analysis

Contact scientist: David Cockburn

	Test	Target reporting time (working days)
1.	Linkage analysis	40

Contact: Kim Flintoff