MEDNIK syndrome (mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratoderma) is an autosomal-recessive disorder caused by bi-allelic mutations in AP1S1, encoding the small σ subunit of the AP-1 complex.
MEDNIK syndrome is caused by mutation of the AP1S1 gene, which codes for the σ1A subunit of adaptor protein complex 1, and directs intracellular trafficking of copper pumps ATP7A and ATP7B.
We solved the pathogenetic mechanism of MEDNIK syndrome, demonstrating that AP1S1 regulates intracellular copper machinery mediated by copper-pump proteins.
We solved the pathogenetic mechanism of MEDNIK syndrome, demonstrating that AP1S1 regulates intracellular copper machinery mediated by copper-pump proteins.
Together, these results confirm AP1S1 as the gene responsible for MEDNIK syndrome and demonstrate a critical role of AP1S1 in development of the skin and spinal cord.
Together, these results confirm AP1S1 as the gene responsible for MEDNIK syndrome and demonstrate a critical role of AP1S1 in development of the skin and spinal cord.
Together, these results confirm AP1S1 as the gene responsible for MEDNIK syndrome and demonstrate a critical role of AP1S1 in development of the skin and spinal cord.
Erythrokeratodermia variabilis 3 (Kamouraska type) or EKV3 is a newly described autosomal recessive disorder observed in patients from the Bas St-Laurent region of Quebec.
Functional characterization of fibroblasts derived from affected individuals closely resembles the abnormal ATP7A trafficking described in MEDNIK syndrome both at baseline and in response to copper treatment.
In the past 2 years (2012-2013), three new autosomal recessive copper metabolism conditions have been recognized: 1) Huppke-Brendel syndrome caused by mutations in an acetyl CoA transporter needed for acetylation of one or more copper proteins, 2) CCS deficiency caused by mutations in the copper chaperone to SODI, and 3) MEDNIK syndrome, which revealed that mutations in the σ1A subunit of adaptor protein complex 1 (AP-1) have detrimental effects on trafficking of ATP7A and ATP7B.