Document Detail

A PEX6-defective peroxisomal biogenesis disorder with severe phenotype in an infant, versus mild phenotype resembling Usher syndrome in the affected parents.
MedLine Citation:
PMID:  11873320     Owner:  NLM     Status:  MEDLINE    
Sensorineural deafness and retinitis pigmentosa (RP) are the hallmarks of Usher syndrome (USH) but are also prominent features in peroxisomal biogenesis defects (PBDs); both are autosomal recessively inherited. The firstborn son of unrelated parents, who both had sensorineural deafness and RP diagnosed as USH, presented with sensorineural deafness, RP, dysmorphism, developmental delay, hepatomegaly, and hypsarrhythmia and died at age 17 mo. The infant was shown to have a PBD, on the basis of elevated plasma levels of very-long- and branched-chain fatty acids (VLCFAs and BCFAs), deficiency of multiple peroxisomal functions in fibroblasts, and complete absence of peroxisomes in fibroblasts and liver. Surprisingly, both parents had elevated plasma levels of VLCFAs and BCFAs. Fibroblast studies confirmed that both parents had a PBD. The parents' milder phenotypes correlated with relatively mild peroxisomal biochemical dysfunction and with catalase immunofluorescence microscopy demonstrating mosaicism and temperature sensitivity in fibroblasts. The infant and both of his parents belonged to complementation group C. PEX6 gene sequencing revealed mutations on both alleles, in the infant and in his parents. This unique family is the first report of a PBD with which the parents are themselves affected individuals rather than asymptomatic carriers. Because of considerable overlap between USH and milder PBD phenotypes, individuals suspected to have USH should be screened for peroxisomal dysfunction.
Annick Raas-Rothschild; Ronald J A Wanders; Petra A W Mooijer; Jeannette Gootjes; Hans R Waterham; Alisa Gutman; Yasuyuki Suzuki; Nobuyuki Shimozawa; Naomi Kondo; Gideon Eshel; Marc Espeel; Frank Roels; Stanley H Korman
Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't     Date:  2002-02-28
Journal Detail:
Title:  American journal of human genetics     Volume:  70     ISSN:  0002-9297     ISO Abbreviation:  Am. J. Hum. Genet.     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-03-08     Completed Date:  2002-04-18     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0370475     Medline TA:  Am J Hum Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1062-8     Citation Subset:  IM    
Department of Human Genetics, Hadassah University Hospital, Jerusalem 91120, Israel.
Data Bank Information
Bank Name/Acc. No.:
OMIM/MIM202370;  MIM214100;  MIM266510;  MIM276900;  MIM276901;  MIM276902;  MIM276903;  MIM276904;  MIM276905;  MIM276906;  MIM601067;  MIM601498;  MIM601539;  MIM602083;  MIM602097;  MIM605472
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MeSH Terms
Adenosine Triphosphatases / genetics*
Cells, Cultured
Child, Preschool
DNA Mutational Analysis
Fatal Outcome
Genetic Complementation Test
Hearing Loss, Sensorineural / genetics*,  physiopathology*
Infant, Newborn
Liver / pathology,  ultrastructure
Peroxisomal Disorders / genetics*,  pathology,  physiopathology*
Retinitis Pigmentosa / genetics*,  physiopathology*
Reg. No./Substance:
EC 3.6.1.-/Adenosine Triphosphatases; EC 3.6.1.-/PEX6 protein, human; EC 3.6.1.-/Pex6 protein, rat

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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