Cloning and characterization of an alternatively spliced gene in proximal Xq28 deleted in two patients with intersexual genitalia and myotubular myopathy

Journal Article · Thu May 01 00:00:00 EDT 1997 · Genomics

DOI:https://doi.org/10.1006/geno.1997.4662· OSTI ID:530744

Laporte, J; Hu, Ling-Jia; Kretz, C ^[1]

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1. Institut de Genetique et de Biologie Moleculaire et Cellulaire, Strasbourg (France); and others

We have identified a novel human gene that is entirely deleted in two boys with abnormal genital development and myotubular myopathy (MTM1). The gene, F18, is located in proximal Xq28, approximately 80 kb centromeric to the recently isolated MTM1 gene. Northern analysis of mRNA showed a ubiquitous pattern and suggested high levels of expression in skeletal muscle, brain, and heart. A transcript of 4.6 kb was detected in a range of tissues, and additional alternate forms of 3.8 and 2.6 kb were present in placenta and pancreas, respectively. The gene extends over 100 kb and is composed of at least seven exons, of which two are non-coding. Sequence analysis of a 4.6-kb cDNA contig revealed two overlapping open reading frames (ORFs) that encode putative proteins of 701 and 424 amino acids, respectively. Two alternative spliced transcripts affecting the large open reading frame were identified that, together with the Northern blot results, suggest that distinct proteins are derived from the gene. No significant homology to other known proteins was detected, but segments of the first ORF encode polyglutamine tracts and proline-rich domains, which are frequently observed in DNA-binding proteins. The F18 gene is a strong candidate for being implicated in the intersexual genitalia present in the two MTM1-deleted patients. The gene also serves as a candidate for other disorders that map to proximal Xq28. 15 refs., 3 figs., 1 tab.

• OSTI ID: 530744
• Journal Information: Genomics, Vol. 41, Issue 3; Other Information: PBD: 1 May 1997
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
HUMAN X CHROMOSOME
CHROMOSOMAL ABERRATIONS
GENETIC MAPPING
PATIENTS
UROGENITAL SYSTEM DISEASES
PHENOTYPE
CONGENITAL DISEASES
HEREDITARY DISEASES
GENES
GENE REGULATION
TISSUE DISTRIBUTION
TRANSCRIPTION
DNA SEQUENCING
DNA-CLONING
STRUCTURE-ACTIVITY RELATIONSHIPS
GENE MUTATIONS
SPLICING
EXONS
AMINO ACIDS
CONTIGS
COSMIDS