(Recessive CMT 2) Nuclear matrix proteins and hereditary diseases

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Genetika. 2005 Mar;41(3):293-8.

Nuclear matrix proteins and hereditary diseases.

Sjakste N, Sjakste T.

University of Latvia, Faculty of Medicine, Riga LV1001 Latvia.

The review summarizes literature data on alterations of structure or

expression of different nuclear matrix proteins in hereditary

syndromes. From the point of view of involvement of nuclear matrix

proteins in etiology and pathogenesis of the disease hereditary

pathologies can be classified in pathologies with pathogenesis

associated with defects of nuclear matrix proteins and pathologies

associated to changes of the nuclear matrix protein spectrum.

The first group includes laminopathies, hereditary diseases with

abnormal nuclear-matrix associated proteins and triplet extension

diseases associated with accumulation of abnormal proteins in the

nuclear matrix.

Laminopathies are hereditary diseases coupled to structural defects

of the nuclear lamina. These diseases include Emery-Dreifuss muscular

dystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy

(DCM) with conduction system disease, familial partial lipodystrophy

(FPLD), autosomal recessive axonal neuropathy (Charcot-Marie-Tooth

disorder type 2, CMT2), mandibuloacral dysplasia (MAD), Hutchison

Gilford Progeria syndrome (HGS), Greenberg Skeletal Dysplasia, and

Pelger-Huet anomaly (PHA).

Most of them are due to mutations in the lamin A/C gene, one - to

mutations in emerin gene, some are associated with mutations in Lamin

B receptor gene. In Werner's, Bloom's, Cockayne's syndromes, Fanconi

anemia, multiple carboxylase deficiency mutations in nuclear matrix

protein or enzyme gene lead to deficient DNA repair, abnormal

regulation of cell growth and differentiation or other specific

metabolic functions.

Proteins with a long polyglutamic tract synthesized in the cells of

patients with dentato-rubral and pallido-luysian atrophy, myotonic

dystrophy and Huntington disease interfere with transcription on the

nuclear matrix. Down's syndrome is a representative of the group of

diseases with altered nuclear matrix protein spectrum.