• autosomal recessive limb-girdle muscular dystrophy type 2Z

This report describes muscular dystrophy, limb-girdle, type 2Z (LGMD2Z), which is a subtype of muscular dystrophy, limb-girdle; LGMD2Z exhibits autosomal recessive inheritance. The human gene implicated in this disease is protein O-glucosyltransferase 1 (POGLUT1), which targets extracellular EGF repeats of various proteins, including NOTCH proteins. There is a single high-scoring ortholog in Drosophila, rumi, for which classical loss of function alleles and RNAi-targeting constructs have been generated. In human, LGMD2Z is also implicated in a second disease, Dowling-Degos disease 4 (MIM:615696).

Multiple UAS constructs of the human Hsap\POGLUT1 gene have been introduced into flies, including wild type and a variant implicated in LGMD2Z. Heterologous rescue (functional complementation) is observed: overexpression of wild-type human POGLUT1 in muscle progenitors rescues the muscle phenotypes of a temperature-sensitive loss-of-function allele of Dmel\rumi; a variant implicated in LGMD2Z exhibits weaker, variable rescue. Variant(s) implicated in human disease tested (as transgenic human gene, POGLUT1): the D233E variant form has been introduced into flies.

At restrictive temperatures, animals homozygous for a temperature-sensitive mutation of Dmel\rumi exhibit decreased numbers of myoblasts and muscle defects at the pupal stage. Adults homozygous for a second temperature-sensitive mutation exhibit eye (rhabdomere) phenotypes at permissive temperatures. Embryos lacking both maternal and zygotic rumi function have a neurogenic phenotype; mitotic clones exhibit the loss of thoracic sensory bristles and margin loss and vein expansion in the wing. Genetic interactions of rumi have been described; see the rumi gene report.

[updated May 2018 by FlyBase; FBrf0222196]