ABSTRACT
There are 25 known genes coding for human selenoproteins, whose expression requires decoding of an UGA codon as the amino acid selenocysteine (Sec) instead of a premature stop. This process is mediated by the interaction of a Sec insertion sequence (SECIS) element in the 3′-untranslated region of selenoprotein mRNAs with SECIS binding protein 2 (SBP2) (Copeland and Driscoll, 1999) (see also Chapter 3). SBP2 is a limiting, obligate factor for selenoprotein synthesis as first shown by absence of selenoprotein synthesis in SBP2-depleted cell lysates with restoration of production by repletion with SBP2. Furthermore, SBP2 is essential for survival as murine Secisbp2 deletion is embryonic lethal (Seeher et al., 2014a). Here, we will describe characteristics and pathogenesis of a human disorder due to mutations in SECISBP2, disrupting synthesis of multiple selenoproteins. The indispensable role of selenoproteins in diverse physiological processes is demonstrated by the
16.1 Introduction .................................................................................................. 343 16.2 Structure and Function of SBP2 ...................................................................344 16.3 Function of Mammalian Selenoproteins ...................................................... 347
16.3.1 Deletion of Secisbp2 ....................................................................... 350 16.4 Disorder Due to Human SECISBP2 Mutations ............................................ 351
16.4.1 Human SBP2 Mutations ................................................................. 351 16.4.2 Biochemistry ................................................................................... 359 16.4.3 Growth and Skeletal Phenotype ..................................................... 359 16.4.4 Hearing Loss ...................................................................................360 16.4.5 Developmental and Neurological Phenotype .................................360 16.4.6 Axial Muscular Dystrophy .............................................................360 16.4.7 Metabolic Phenotype ...................................................................... 361 16.4.8 Azoospermia with Spermatogenic Maturation Arrest ................... 362 16.4.9 Cutaneous Photosensitivity ............................................................. 362 16.4.10 Impaired T-Cell Proliferation and Abnormal Cytokine Production ... 363 16.4.11 Effect of Treatment .........................................................................364
