An infant with deletion of the distal long arm of chromosome 15 (q26.1→qter) and loss of insulin‐like growth factor 1 receptor gene

Abstract

We report on an infant with a previously undescribed chromosome 15 deletion (q26.1----qter) and compare the clinical findings with those of 7 reported patients with deletions of distal 15q, as well as ring chromosome 15 syndrome patients. Most of the patients with deletions of distal 15q, including our patient, have intrauterine growth retardation (IUGR), microcephaly, abnormal face and ears, micrognathia, highly arched palate, renal abnormalities, lung hypoplasia, failure to thrive, and developmental delay/mental retardation. Several genes have been assigned to the 15q25----qter region, including insulin-like growth factor 1 receptor (IGF1R). DNA analysis from our patient documented the loss of one IGF1R gene copy. Our study further localizes the IGF1R gene distal to the 15q26.1 band. It is interesting to speculate that the severe IUGR and postnatal growth deficiency of our patient and other patients with similar chromosome 15 deletions are related to the loss of an IGF1R gene copy which may lead to an abnormal number and/or structure of the receptors.

New molecular mechanisms of GH resistance

“…A series of studies involving targeted disruption of genes for various components of the IGF axis indicated that knockout of the genes for either IGF-I or IGF-II resulted in a 40% reduction in fetal growth, while knockouts of both genes or the genes for the IGF-I receptor (IGFR) led to a 55% decrease in fetal size and, generally, demise of the animal shortly after death (24). The possibility that abnormalities of IGFR could result in some combination of intrauterine and postnatal growth failure was supported by observations in patients with deletions of chromosome 15q and consequent haploinsufficiency for IGFR (25). Interpretation of the phenotypes of such patients is complicated, however, by the loss of contiguous genes which might contribute to the growth characteristics.…”

Overgrowth and trisomy 15q26.1-qter including the IGF1 receptor gene: report of two families and review of the literature

“…Interestingly a large family with autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia and distinctive facies was recently reported and a gene locus was identified in 15q26. 24 The aggrecan gene (AGC1), a chondroitin sulphate proteoglycan that was a possible candidate gene, was excluded. 25 In conclusion, we report on four further cases of overgrowth associated with trisomy 15q26.1-qter including the IGF1R locus.…”

Mono-allelic expression of the IGF-I receptor does not affect IGF responses in human fibroblasts

“…There are only 12 cases documented with a mono-allelic loss of the IGF1R gene in children with deletions of the distal long arm of chromosome 15. The clinical findings of the patient presented in this work in comparison with those five patients showing a 15q26.1-qter (17,18,20,23) indicate that intrauterine growth retardation (IUGR), high-arched palate, abnormal ears, micrognathia, cardiac abnormality, lung hypoplasia, developmental delay, and postnatal growth failure are the major signs and symptoms present in these children (observed in at least 50% of the patients; Table 1). Since heterozygous Igf1r knockout mice did not show any discernible phenotype (7) it can be speculated that mono-allelic loss of genes located distally from the IGF1R may contribute to the severe disease phenotype of the patients.…”