Abstract
A rare type of familial isolated GH deficiency (type 1A) is caused by homozygosity for deletion of the structural gene for GH (GH-N). This gene is normally located on the 5' end of the 40-kb GH gene cluster (5'-GH(N)-CS(L)-CS(A)-GH(V)-CS(B)-3'). Six of eight such deletions we have studied differed in either their size (6.7 versus 7.6-kb) or in their pattern of restriction fragments which contain the non-deleted components of the cluster. Since these differences suggested GH-N deletions had occurred multiple different times we analyzed the DNA sequence of a novel fragment produced by a deletion to determine the mechanism of the deletion. The DNA studied was from a subject with a 7.6-kb deletion in which the BAM HI derived 8.3-kb genomic fragment normally containing the CS-L gene was replaced by a unique 9.3-kb fragment. We inferred this unique fragment resulted from fusion of sequences which normally flank the GH-N gene. The complete DNA sequence of the 9.3-kb fragment was determined and the point of transition from sequences normally 5' to GH-N to those normally 3' was detected. The junction of these flanking sequences occurred within the 29-bp sequence TCAGCAGAAGTGGAATTCAGGAGTGAATC. Perfect repeats of these 29 bases lie 497-bp 5' and 7082-bp 3' to the GH-N cap site. Since the 7.6-kb genornic deletions would result from unequal crossing-over between these two homologous copies these repeats may comprise hotspots for recurrence of such deletions.
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Phillips, J., Chen, E. & Seeburg, P. 845 MOLECULAR BASIS OF GROWTH HORMONE (GH) GENE DELETIONS. Pediatr Res 19, 251 (1985). https://doi.org/10.1203/00006450-198504000-00875
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DOI: https://doi.org/10.1203/00006450-198504000-00875