Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-7-8
pubmed:abstractText
Hypomyelinating leukodystrophies (HMLs) are disorders involving aberrant myelin formation. The prototype of primary HMLs is the X-linked Pelizaeus-Merzbacher disease (PMD) caused by mutations in PLP1. Recently, homozygous mutations in GJA12 encoding connexin 47 were found in patients with autosomal-recessive Pelizaeus-Merzbacher-like disease (PMLD). However, many patients of both genders with PMLD carry neither PLP1 nor GJA12 mutations. We report a consanguineous Israeli Bedouin kindred with clinical and radiological findings compatible with PMLD, in which linkage to PLP1 and GJA12 was excluded. Using homozygosity mapping and mutation analysis, we have identified a homozygous missense mutation (D29G) not previously described in HSPD1, encoding the mitochondrial heat-shock protein 60 (Hsp60) in all affected individuals. The D29G mutation completely segregates with the disease-associated phenotype. The pathogenic effect of D29G on Hsp60-chaperonin activity was verified by an in vivo E. coli complementation assay, which demonstrated compromised ability of the D29G-Hsp60 mutant protein to support E. coli survival, especially at high temperatures. The disorder, which we have termed MitCHAP-60 disease, can be distinguished from spastic paraplegia 13 (SPG13), another Hsp60-associated autosomal-dominant neurodegenerative disorder, by its autosomal-recessive inheritance pattern, as well as by its early-onset, profound cerebral involvement and lethality. Our findings suggest that Hsp60 defects can cause neurodegenerative pathologies of varying severity, not previously suspected on the basis of the SPG13 phenotype. These findings should help to clarify the important role of Hsp60 in myelinogenesis and neurodegeneration.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-10482535, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-10520936, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-10540652, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-11050098, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-11093273, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-11395418, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-11723390, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-11884745, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-11898127, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-12566514, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-12925358, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-14506246, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-15192806, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-15627202, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-15927499, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-16133422, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-16469273, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-16675490, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-16685644, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-16707726, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-16805775, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-16815381, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-16887805, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-17072495, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-17115121, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-17150954, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-1731198, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-17420924, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-17485245, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-17486441, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-17489689, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-17502481, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-17536179, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-17823127, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-17974614, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-18094336, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-18400758, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-2528694, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-2563997, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-2645524, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-7955429, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-8549659, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-9067800, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-9285585, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-9476895, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-9563826, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-9633728, http://linkedlifedata.com/resource/pubmed/commentcorrection/18571143-9635427
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1537-6605
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
83
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
30-42
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
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