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)
- Baylor College of Medicine, Houston, TX (United States)
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 microphthalmia, 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 {approx}2.6 kb in all tissues examined, with weaker expression of {approx}1.2- and {approx}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. 25 refs., 4 figs.
- OSTI ID:
- 476770
- Journal Information:
- Genomics, Vol. 34, Issue 2; Other Information: PBD: 1 Jun 1996
- Country of Publication:
- United States
- Language:
- English
Similar Records
Microphthalmia and linear skin defects (MLS) and focal dermal hypoplasia of Goltz (FDHG); Clinical cytogenetic, and molecular studies
Microphthalmia with linear skin defects (MLS) syndrome: Clinical, cytogenetic, and molecular characterization
Related Subjects
BASIC STUDIES
CYTOCHROMES
GENE MUTATIONS
GENE REGULATION
DNA SEQUENCING
TRANSCRIPTION
STRUCTURE-ACTIVITY RELATIONSHIPS
GENETIC MAPPING
TISSUE DISTRIBUTION
HUMAN X CHROMOSOME
LETHAL MUTATIONS
CHROMOSOMAL ABERRATIONS
MALES
HEREDITARY DISEASES
SKIN DISEASES
PHENOTYPE
CONGENITAL DISEASES
AMINO ACID SEQUENCE
MICE
CONTIGS
LIGASES
MITOCHONDRIA
POLYMERASE CHAIN REACTION