ACAN biallelic variants in a girl with severe idiopathic short stature
ACAN biallelic variants in a girl with severe idiopathic short stature
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严重特发性身材矮小女孩的 ACAN 双等位基因变异
DOI：
10.1038/s10038-022-01030-3
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发表时间：
2022
期刊：
影响因子：
3.5
通讯作者：
Ogata T
中科院分区：
文献类型：
--
作者：
Masunaga Y;Ohkubo Y;Nishimura G;Ueno T;Fujisawa Y;Fukami M;Saitsu H;Ogata T
虽然ACAN杂合性功能丧失变异常导致特发性矮小(ISS)表型，但尚无ACAN双等位基因功能丧失变异引起ISS表型的报道。我们遇到了一位4岁半的日本女孩，身高80.4 cm(−5.2 SD)，体重11.4 kg(−1.9 SD)，头围48.7 cm(−0.6 SD)，臂展/身高比1.0(+1.1 SD)。内分泌检查和骨骼测量均未发现异常。全外显子组测序发现ACAN基因有罕见的双等位变异，即NM_013227.4：C.4214delC：P.(Pro1405Leufs*3)来自其父亲和身材矮小的祖父(分别为−2.9和−2.0 SD)和NM_013227.4：C.7124 A>；G：p(−2.1和−3.0 SD)遗传自其母亲和外祖母。移码变异体经历了无义介导的mRNA衰变，错义变异体被评估为具有高致病性。这一结果首次暗示ACAN双等位基因功能丧失变异可导致严重的ISS表型。
AlthoughACANheterozygous loss-of-function variants often cause idiopathic short stature (ISS) phenotype, there is no report describing ISS phenotype caused byACANbiallelic loss-of-function variants. We encountered a 4 1/12-year-old Japanese girl with a height of 80.4 cm (−5.2 SD), a weight of 11.4 kg (−1.9 SD), a head circumference of 48.7 cm (−0.6 SD), and an arm span/height ratio of 1.0 (+1.1 SD). Endocrine studies and bone survey showed no abnormal findings. Whole exome sequencing revealed biallelic rare variants inACAN, i.e., NM_013227.4:c.4214delC:p.(Pro1405Leufs*3) derived from her father and paternal grandfather with short stature (−2.9 and −2.0 SD, respectively) and NM_013227.4:c.7124 A>G:p.(Gln2375Arg) inherited from her mother and maternal grandmother with short stature (−2.1 and −3.0 SD, respectively). The frameshift variant underwent nonsense mediated mRNA decay, and the missense variant was assessed to have high pathogenicity. The results imply for the first time thatACANbiallelic loss-of-function variants can cause severe ISS phenotype.
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影响因子：
3.2
作者：
Gerver, Willem J. M.;Gkourogianni, Alexandra;Wit, Jan M.
通讯作者：
Wit, Jan M.
影响因子：
5.8
作者：
Nilsson, Ola;Guo, Michael H.;Dauber, Andrew
通讯作者：
Dauber, Andrew
影响因子：
1.4
作者：
Bonioli, E;Tarò, M;Coviello, DA
通讯作者：
Coviello, DA
影响因子：
4.6
作者：
Hauer NN;Sticht H;Boppudi S;Büttner C;Kraus C;Trautmann U;Zenker M;Zweier C;Wiesener A;Jamra RA;Wieczorek D;Kelkel J;Jung AM;Uebe S;Ekici AB;Rohrer T;Reis A;Dörr HG;Thiel CT
通讯作者：
Thiel CT
DOI：
10.1007/bf01912484
发表时间：
1989-06-01
期刊：
JAPANESE JOURNAL OF HUMAN GENETICS
影响因子：
--
作者：
MATSUURA, S;KAJII, T
通讯作者：
KAJII, T