Non-Synonymous IGFALS Allelic Variants (ns-Av), Associated with Diminished Levels of IGF-I, IGFBP-3 and ALS, are Found in Nonfamilial (Nf) But Not in Familial (F) Idiopathic Short Stature (ISS) Children

ALICIA S. MARTÍNEZ; PAULA A, SCAGLIA; ANA C. KESELMAN; MARIA GABRIELA ROPELATO; MARIA GABRIELA BALLERINI; SONIA V. BENGOLEA; VIVIANA PIPMAN; RODOLFO A. REY; JUAN J HEINRICH; HÉCTOR G. JASPER; HORACIO M. DOMENÉ

Cartagena de Indias

Congreso; XXII Annual Meeting of the Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP); 2011

Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP)

Non-Synonymous IGFALS Allelic Variants (ns-Av), Associated with Diminished Levels of IGF-I, IGFBP-3 and ALS, are Found in Nonfamilial (Nf) But Not in Familial (F) Idiopathic Short Stature (ISS) Children A. Martínez1, P.A. Scaglia1, A. Keselman1, M.G. Ropelato1,M.G. Ballerini1, S.V. Bengolea2, V. Pipman3, R. Rey1,J.J. Heinrich1, H. Jasper1, H. Domene1 ¹Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) y Hospital de Niños R. Gutiérrez Centro de Investigaciones Endocrinológicas (CEDIE) y División de Endocrinología; ²Hospital Fernández-Pediatria; ³Hospital Tornú-Pediatria, Buenos Aires, Argentina Introduction: Low levels of IGF-I are found in about 30% of ISS children and some of them present heterozygous ns-AV-IGFALS allelic variants. Aim: Our aim was to identify potential carriers of ns-AV. Methods: Height (H-SDS), target adjusted height (TAHSDS), were collected in 68 ISS prepubertal children, classified as For NF and according to IGF-I levels (normal or low). Serum levels of IGF-I, IGFBP-3 and ALS were determined and the IGFALS gene was sequenced. Results: NF were significantly shorter than F children,but their levels of IGF-I, IGFBP-3 and ALS were not different. Those presenting low IGF-I had reduced levels of IGFBP-3 and ALS, but did not differ in H-SDS or TAH-SDS. ns-AV-IGFALS were present in 6/34 NF vs. 2/34 F (p NS), but if low IGF-I and IGFBP-3 were also considered, IGFALS ns-AV were present in 5/34 NF and 0/34 F (p = 0.02). Conclusion: These findings suggest that the NF subgroup of ISS children with reduced levels of IGF-I and IGFBP-3, would be the most likely candidates for genotyping the IGFALS gene searching for ns-AV. F-ISS NF-ISS Fv vs NF-ISS (p) Normal IGF-I ISS Low IGF-I ISS Normal vs low IGF-I ISS (p) ISS with ns-AV ISS without ns-AV With vs without ns-AV (p) N 34 34 44 24 8 60 CA (y) 8,18±2,57 8,57±3,24 NS 8,66±3,12 7,85±2,45 NS 8,04±2,11 8,42±3,01 NS H-SDS -2,65±0,45 -2,96±0,49 0.0080 -2,77±0,57 -2,86±0,31 NS -2,94±0,31 -2,78±0,51 NS TAH-SDS -0,97±0,47 -2,38±0,58 - -1,61±0,87 -1,79±0,91 NS -2,17±0,74 -1,61±0,89 NS IGF-I (SDS) -1,20±1,33 -1,84±1,45 NS -0,67±0,82 -3,07±0,85 - -2,16±1,93 -1,43±1,33 NS IGFBP-3 (SDS) -0,93±0,92 -1,05±1,45 NS -0,67±0,99 -1,36±1,59 0.0313 -2,09±1,58 -0,85±1,08 0.0052 ALS (SDS) -1,23±1,17 -1,62±1,58 NS -1,00±1,08 -2,2±1,59 0.0005 -2,78±1,77 -1,24±1,25 0.0028 ns-AV 2/34 6/34 NS 3/44 5/24 NS Follow up N 21 N 21 T test (p) N 25 N 17 T test (p) ΔH-SDS 0,19±0,31 0,49±0,34 0.0046 0,39±0,39 0,25±0,28 NS ΔTime (y, length of prepubertal follow up period) 2,06±1,05 2,68±1,20 NS 2,49±1,23 2,18±1,06 NS