Coutinho Debora C, Coletta Rocio R D, Costa Elaine M F, Pachi Paulo R, Boguszewski Margaret C S, Damiani Durval, Mendonca Berenice B, Arnhold Ivo J P, Jorge Alexander A L
Unidade de Endocrinologia do Desenvolvimento, Unidade de Endocrinologia do Desenvolvimento, 05403-900 Sao Paulo, Brazil.
J Clin Endocrinol Metab. 2007 Dec;92(12):4889-92. doi: 10.1210/jc.2007-1661. Epub 2007 Sep 25.
Few children born small for gestational age (SGA) with IGF1 mutations have been reported. One of these patients presented a mutation at 3' untranslated region (UTR) at exon 6, probably affecting the polyadenylation process.
The objective of the study was to sequence the IGF1 gene of children born SGA.
IGF1 (exons 1-6) was directly sequenced in 53 SGA children without catch-up growth. Allelic variant frequency of the identified IGF1 polymorphisms was assessed in a total of 145 SGA children and in 180 controls born with adequate weight and length and adult height sd score greater than -2.
No mutations were identified in the IGF1 coding regions in SGA children. In contrast, six allelic variants were identified in the upstream core polyadenylation signal located in IGF1 3' UTR at exon 6. The frequency of the different allelic variants was similar in SGA children and controls. It is noteworthy that the same allelic variant, previously described as causing severe IGF1 deficiency, was also observed in homozygous (n = 4) and heterozygous state (n = 6) in normal height controls, corresponding to 4% of studied alleles. The three most frequently identified allelic variants of IGF1 3' UTR showed no effect on height sd score of adult controls as well as on birth characteristics in SGA children.
The polymorphisms identified in the upstream core polyadenylation signal at IGF1 exon 6 do not cause IGF1 deficiency as well as pre- and postnatal growth impairment, in contrast to previously reported data.
据报道，携带胰岛素样生长因子1（IGF1）突变的小于胎龄儿（SGA）患儿数量很少。其中一名患者在第6外显子的3'非翻译区（UTR）出现突变，可能影响多聚腺苷酸化过程。
本研究的目的是对SGA患儿的IGF1基因进行测序。
对53例无追赶生长的SGA患儿的IGF1（外显子1 - 6）进行直接测序。在总共145例SGA患儿以及180例出生时体重和身长正常且成年身高标准差评分大于-2的对照中评估所鉴定的IGF1多态性的等位基因变异频率。
在SGA患儿的IGF1编码区未发现突变。相反，在位于第6外显子的IGF1 3'UTR的上游核心多聚腺苷酸化信号中鉴定出六个等位基因变异。SGA患儿和对照中不同等位基因变异的频率相似。值得注意的是，在正常身高对照中也观察到相同的等位基因变异，之前描述该变异会导致严重的IGF1缺乏，在纯合子（n = 4）和杂合子状态（n = 6）下均有出现，占研究等位基因的4%。IGF1 3'UTR最常鉴定出的三个等位基因变异对成年对照的身高标准差评分以及SGA患儿的出生特征均无影响。
与先前报道的数据相反，在IGF1第6外显子上游核心多聚腺苷酸化信号中鉴定出的多态性不会导致IGF1缺乏以及产前和产后生长障碍。
