The PACS-1 protein has a putative role in the localization of trans-Golgi network (TGN) membrane proteins. Mouse and rat homologs have been identified and studies of the homologous rat protein indicate a role in directing TGN localization of furin by binding to the protease's phosphorylated cytosolic domain. In addition, the human protein plays a role in HIV-1Nef-mediated downregulation of cell surface MHC-I molecules to the TGN, thereby enabling HIV-1 to escape immune surveillance.[3]
The first two cases were identified in early 2011 by doctors in the Netherlands.[5] As of late 2014, there were 20 cases identified worldwide.[7]
Diagnosis is typically done using full genome or exome sequencing.[8] There are likely several more cases that will eventually be reported as knowledge of the mutation spreads and testing becomes more accessible.
Observed and reported traits
Individuals with the mutation have been reported to have similar facial features, such as:
Widely spaced eyes and low-set ears
Down-slanting eye corners and mild uni-brow
Highly arched eyebrows and long eyelashes
Rounded “button” nose with a flat bridge
Wide mouth with down-turned corners
Thin upper lip and widely spaced teeth
Other common traits reported by care givers of affected individuals are:
Slow growth resulting in below average height and weight
Prognosis and treatment
In combination, these traits affect walking, talking, feeding, and learning skills. No impact on life expectancy has been found. As with many developmental disabilities, there is no "cure".
In order to improve quality of life and enhance life skills of affected individuals, care givers have found a number of tools and strategies. It is important to note that all of these may not be applicable to a particular individual, and reported effectiveness has varied. It is recommended to consult with a physician prior to initiating any form of treatment.[9]
↑Stove V, Naessens E, Stove C, Swigut T, Plum J, Verhasselt B (Oct 2003). "Signaling but not trafficking function of HIV-1 protein Nef is essential for Nef-induced defects in human intrathymic T-cell development". Blood. 102 (8): 2925–32. doi:10.1182/blood-2003-03-0833. PMID12855553.
↑Wan L, Molloy SS, Thomas L, Liu G, Xiang Y, Rybak SL, Thomas G (Jul 1998). "PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization". Cell. 94 (2): 205–16. doi:10.1016/S0092-8674(00)81420-8. PMID9695949.
Leavitt SA, SchOn A, Klein JC, Manjappara U, Chaiken IM, Freire E (Feb 2004). "Interactions of HIV-1 proteins gp120 and Nef with cellular partners define a novel allosteric paradigm". Current Protein & Peptide Science. 5 (1): 1–8. doi:10.2174/1389203043486955. PMID14965316.
Joseph AM, Kumar M, Mitra D (Jan 2005). "Nef: "necessary and enforcing factor" in HIV infection". Current HIV Research. 3 (1): 87–94. doi:10.2174/1570162052773013. PMID15638726.
Wan L, Molloy SS, Thomas L, Liu G, Xiang Y, Rybak SL, Thomas G (Jul 1998). "PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization". Cell. 94 (2): 205–16. doi:10.1016/S0092-8674(00)81420-8. PMID9695949.
Hirosawa M, Nagase T, Ishikawa K, Kikuno R, Nomura N, Ohara O (Oct 1999). "Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain". DNA Research. 6 (5): 329–36. doi:10.1093/dnares/6.5.329. PMID10574461.
Blagoveshchenskaya AD, Thomas L, Feliciangeli SF, Hung CH, Thomas G (Dec 2002). "HIV-1 Nef downregulates MHC-I by a PACS-1- and PI3K-regulated ARF6 endocytic pathway". Cell. 111 (6): 853–66. doi:10.1016/S0092-8674(02)01162-5. PMID12526811.
