No abstract

SummaryDeletions and point mutations of the growth hormone (GH) receptor gene (GHR) have been identified in patients with Laron syndrome. We report the first detection of the GHR mutation among Japanese patients with Laron syndrome. Using the Japanese female patient's genomic DNA as a template, all exons and flanking portions of introns of GHR were amplified by polymerase chain reaction (PCR). Sequencing of the PCR products showed that the patient was homozygous for a G to A substitution at the first position of intron 4. This substitution was same as that detected in a Spanish patient and a north European patient. The base change occurred at the 5' splice consensus sequence of intron 4, resulting in the abolition of a BanI restriction site. Since this substitution was not detected by a BanI restriction analysis in 85 control individuals, it is more likely a disease-related splice mutation than a polymorphism. The mutation in our patient was predicted to destroy the original 5" splice site of intron 4 of GHR and to produce a new cryptic splice site, leading to abnormal mRNA processing and a lack of GH binding activity of GH-binding protein (GHBP).

A 59-year-old female with 20-year history of slowly progressing muscle atrophy and sensory disturbance of upper extremities showed short stature, scoliosis, hunger type of sensory dissociation of the upper extremities and pyramidal tract sign of the lower extremities. Magnetic resonance imaging (MRI) clarified hypoplasia of the anterior pituitary lobe, Arnold-Chiari malformation and cervical syringomyelia. Insulin and arginine stimulating tests revealed partial type of isolated growth hormone (GH) deficiency but GHgene analysis detected no defects of GHgenes. It was considered to be a rare case of non-hereditary hypopituitarism with Chiari malformation and syringomyelia not associated with perinatal injury, namely a midline anomaly syndrome. (Internal Medicine 37: 674-677, 1998)