title: Cloning and characterization of a putative human holocytochrome c-type synthetase gene (HCCS) isolated from the critical region for microphthalmia with linear skin defects (MLS).
abstract: Microphthalmia with linear skin defects syndrome (MLS) is an X-linked male-lethal disorder associated with X chromosomal rearrangements resulting in monosomy from Xpter to Xp22. Features include micro- phthalmia, sclerocornea, linear skin defects, and agenesis of the corpus callosum. Using a cross-species conservation strategy, an expressed sequence from the 450- to the 550-kb MLS critical region on Xp22 was identified by screening a human embryo cDNA library. Northern analysis revealed a transcript of approximately 2.6 kb in all tissues examined, with weaker expression of approximately 1.2- and approximately 5.2-kb transcripts. The strongest expression was observed in heart and skeletal muscle. Sequence analysis of a 3-kb cDNA contig revealed an 807-bp open reading frame encoding a putative 268-amino-acid protein. Comparison of the sequence with sequences in the databases revealed homology with holocytochrome c-type synthetases, which catalyze the covalent addition of a heme group onto c-type cytochromes in the mitochondria. The c-type cytochromes are required for proper functioning of the electron transport pathway. The human gene (HGMW-approved symbol HCCS) and the corresponding murine gene characterized in this paper are the first mammalian holocytochrome c-type synthetases to be described in the literature. Because of the lack of a neuromuscular phenotype in MLS, it is uncertain whether the deletion of a mitochondrial holocytochrome synthetase would contribute to the phenotype seen in MLS. The expression pattern of this gene and knowledge about the function of holocytochrome synthetases, however, suggest that it is a good candidate for X-linked encephalomyopathies typically associated with mitochondrial dysfunction.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA.
authors.forename: L
authors.initials: L
authors.lastname: Schaefer
authors.forename: A
authors.initials: A
authors.lastname: Ballabio
authors.forename: H Y
authors.initials: HY
authors.lastname: Zoghbi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000201:enzymology; D002460:Cell Line; D002874:Chromosome Mapping; D003360:Cosmids; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D015723:Gene Library; D005804:Genes, Lethal; D006801:Humans; D008190:Lyases / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D008214:Lymphocytes; D008297:Male; D051379:Mice; D008850:Microphthalmos / Q000201:enzymology / Q000235:genetics*; D008969:Molecular Sequence Data; D009006:Monosomy; D009492:Neurospora crassa / Q000201:enzymology; D012333:RNA, Messenger / Q000096:biosynthesis; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D017386:Sequence Homology, Amino Acid; D012868:Skin Abnormalities; D012984:Software; D014158:Transcription, Genetic; D014960:X Chromosome
chemical_list: D012333:RNA, Messenger; D008190:Lyases; C031581:cytochrome C synthetase