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Transfer of a mitochondrial DNA fragment to MCOLN1 causes an inherited case of mucolipidosis IV
Author(s) -
Goldin Ehud,
Stahl Stefanie,
Cooney Adele M.,
Kaneski Christine R.,
Gupta Surya,
Brady Roscoe O.,
Ellis James R.,
Schiffmann Raphael
Publication year - 2004
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20094
Subject(s) - biology , exon , genetics , mitochondrial dna , splice site mutation , intron , stop codon , rna splicing , mutation , splice , microbiology and biotechnology , gene , alternative splicing , rna
A patient with mucolipidosis‐IV heterozygous for two mutations in MCOLN1 expressed only her father's cDNA mutation c.1207C>T predicting an R403C change in mucolipin. She inherited a 93bp segment from mitochondrial NADH dehydrogenase 5 ( MTND5 ) from her mother that was inserted in‐frame prior to the last nucleotide of exon 2 of MCOLN1 (c.236_237ins93). This alteration abolished proper splicing of MCOLN1 . The splice site at the end of the exon was not used due to an inhibitory effect of the inserted segment, resulting in two aberrant splice products containing stop codons in the downstream intron. These products were eliminated via nonsense‐mediated decay. This is the first report of an inherited transfer of mitochondrial nuclear DNA causing a genetic disease. The elimination of the splice site by the mitochondrial DNA requires a change in splicing prediction models. Human Mutation 24:460–465, 2004. © 2004 Wiley‐Liss, Inc.