ICEECE2012 Poster Presentations Paediatric endocrinology (47 abstracts)
Two novel IGF1R gene heterozygous mutations in two unrelated children with pre and postnatal growth retardation, and microcephaly
G. Guercio , D. Warman , M. Aziz , C. Riu , M. Aguiar , M. Juanes , R. Marino , M. Ciaccio , E. Berensztein , E. Chaler , M. Rivarola & A. Belgorosky
Hospital de Pediatria Garrahan, Buenos Aires, Argentina.
Several IGF1R gene mutations have been described as a cause of growth retardation due to IGF1 insensitivity. The IGF1R gene was analyzed in two children suspected to have IGF1 insensitivity. Both were born small for gestational age (SGA) and showed no postnatal catch-up growth. Both patients presented microcephaly and developmental delay. A boy (P1) was born at 37 weeks, birth weight was 1900 g (−2.98 SDS) and body length 42 cm (−4.7 SDS). At 18 months chronological age (CA), height SDS was −2.17, weight SDS −3.3 and head circumference SDS −4. At 2.75 years CA, bone age (BA) was 1.5 years. He showed a mild dysmorphic phenotype. External genitalia and scrotal testes were normal. Basal serum GH (8 ng/ml), IGF1 (+2.94 SDS) and IGFBP3 (+3.37 SDS) were high for sex and age. A girl (P2) was born at 38 weeks, birth weight was 2650 g (−1.4 SDS), and body length 44 cm (−3.3 SDS). At 3.2 years CA, height SDS was −2.95, weight SDS −2.73 and head circumference SDS −2.2. At 2.6 years CA, BA was 1 years. She presented a Klippel Feil malformation. Basal serum GH (8.51 ng/ml) was high but serum IGF1 (+0.42 SDS) and IGFBP3 (+0.61 SDS) were normal for sex and age. No chromosome 15 anomalies were detected. Two novel heterozygous mutations, de novo R1256S (P1) and R1337C (P2) were detected in exon 21 of the IGF1R gene. The aminoacid substitutions were located at highly conserved aminoacid residues in the protein. These mutations were predicted to affect protein function using the sequence homology based SIFT tool and the structure-based PolyPhen approach. Given that phenotype, serum IGF1 and serum GH in IGF1R haploinsufficiency are quite variable, IGF1R molecular studies should be considered in children with an undiagnosed history of SGA without postnatal catch-up growth, and microcephaly.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.
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Endocrine Abstracts
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