What causes ISPD-associated congenital muscular dystrophy (MDDGA7)?

Updated: Jul 03, 2019
  • Author: Emad R Noor, MBChB; Chief Editor: Amy Kao, MD  more...
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Answer

Recessive mutations in the isoprenoidsynthetase domain (ISPD) may be a relatively common cause of Walker-Warburg syndrome, representing about 10% of cases. [39, 40]

While not a glycotransferase, mutations impair the ability of POMT1/2 to transfer O-mannose. This leads to a reduction in functional glycosylation of α-dystroglycan and loss of its laminin-binding epitope.

It was initially described in severe cases of Walker-Warburg syndrome and in families with patients having cobblestone lissencephaly. [41]

It can also result in limb-girdle muscular dystrophy with or without mental retardation, limb-girdle muscular dystrophy with cerebellar involvement, and congenital muscular dystrophy without mental retardation. [42]

Other features include progressive loss of ambulation usually in the mid teens, muscle pseudohypertrophy, and respiratory and cardiac involvement.

Muscle biopsy shows reduced or absent α-dystroglycan immunohistochemical labeling.


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