MOLECULAR DIAGNOSIS AND ENDOCRINE EVALUATION OF A PATIENT WITH A HOMOZYGOUS 7.0 KB DELETION OF THE GROWTH-HORMONE (GH) GENE-CLUSTER - RESPONSE TO BIOSYNTHETIC GH THERAPY

A significant proportion of cases of GH deficiency (5-30%) may be due to genetic causes. At least four Mendelian types of isolated GH defici ency (IGHD) have been delineated based on the mode of inheritance and the degree of GH deficiency, with IGHD type IA being the most severe. A 2 year-old girl, the second child of consanguineous parents, with sh ort stature was diagnosed with IGHD type IA, The analysis of the genom ic DNA of this patient, performed by polymerase chain reaction (PCR) a mplification of the flanking regions of the GH-1 gene, showed a homozy gous deletion of 7.0 kb of sequence including the GH-1 gene, She was t reated with biosynthetic GH resulting in long-lasting catch-up growth during at least three years, despite a clinically irrelevant appearanc e of low binding capacity GH antibodies. Growth hormone-binding protei n (GHBP) levels were normal at the time of diagnosis. In addition, GHB P plasma levels did not show any significant change during the three y ears of therapy with GH. Diagnosis of carrier status in family relativ es was done by genotyping GH gene alleles by PCR amplification from bl ood spots on filter paper.