by us in families 4 and 5 5 17 a new splice site mutation with a t to c transition of the second base of the intron 3 donor splice site was detected in family 2 restriction fragment analysis of a 327 bp dna fragment 5816 u2013 6140 containing the complete intron 3 with n1aiii family 1 and mvni family 2 fig2 and with ddei families 4 and 5 5 17 detected the mutation in all affected but in no unaffected individuals of the 4 families ectopic transcript analysis of lymphocyte mrna was performed in the proband of family 5 and revealed the presence of a shortened mrna lacking exon 3 fig4 lane 1 5 in family 3 we detected a novel heterozygous point mutation in exon 4 with a g to t transversion at position 6191 co segregation with gh deficiency were proven by restriction fragment analysis with maeii demonstrating heterozygote loss of the maeii recognition site in all affected individuals fig3 because the g 6191 to t mutation was inside an exonic motive that was homologous to a sequence which was reported to act as an exonic splicing enhancer in the human igm gene 21 we performed ectopic transcript analysis of peripheral lymphocyte rna the main gh mrna fragment found was identical to controls excluding a defect of primary rna splicing fig4 lane 2 the missense mutation results in an amino acid exchange from valine to phenylalanine at position 110 of the mutant growth hormone v110f gh the alignment of gh sequences revealed that val 110 is highly conserved in mammalian and also in several non mammalian gh fig5 the clinical characteristics of the affected children at the time of diagnosis are summarized in table 1 the sdscores were taken from prader et al 22 for better comparison.