Skeletal dysplasia

Gene: ATP7A

Green List (high evidence)

ATP7A-related copper transport disorders are classically separated in three pathologies according to their severity, all inherited in an X-linked recessive manner: Menkes disease (MD, OMIM #309400) which represent more than 90% of cases; occipital Horn Syndrome (OHS, OMIM #304150) and ATP7A-related distal motor neuropathy also named X-linked distal spinal muscular atrophy-3 (SMAX3, OMIM #300489). Although there is no clear cut correlation between Cu and ceruloplasmin levels in ATP7A related disorders, these three entities probably represent a continuum partly depending on residual functional ATP7A protein.

Created: 25 May 2021, 10:43 a.m. | Last Modified: 25 May 2021, 10:43 a.m.

Panel Version: 0.7670

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Menkes disease MIM#309400; Occipital horn syndrome MIM#304150; Spinal muscular atrophy, distal, X-linked 3, MIM# 300489

Publications

• 20170900
• 33137485
• 31969342
• 31558336

Green List (high evidence)

Well-established gene-disease association. Menkes disease and Occipital horn syndrome are caused by an inborn error of copper metabolism.
Sources: NHS GMS

Created: 1 Feb 2021, 5:13 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Menkes disease MIM#309400; Occipital horn syndrome MIM#304150; disorder of copper matabolism

Publications

• 7842019
• 8981948

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Menkes disease results from complete loss of transcript, while minimal residual transcript causes the milder OHS. Females have been described with the Occipital horn syndrome phenotype (OMIM).

Missense variants usually lead to splicing defects (PMID: 21221114)

Created: 27 Nov 2020, 3:09 a.m. | Last Modified: 27 Nov 2020, 3:09 a.m.

Panel Version: 0.5474

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Occipital horn syndrome, 304150; X-linked recessive Menkes disease, 309400 Spinal muscular atrophy, distal, X-linked 3, 300489

Publications

• PMID: 21221114