Complex Modes of Inheritance in Hereditary Red Blood Cell Disorders: A Case Series Study of 155 Patients.
Complex Modes of Inheritance in Hereditary Red Blood Cell Disorders: A Case Series Study of 155 Patients.
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遗传性红细胞疾病中遗传的复杂模式：155例患者的病例系列研究。
DOI：
10.3390/genes12070958
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发表时间：
2021-06-23
期刊：
影响因子：
3.5
通讯作者：
Russo R
中科院分区：
文献类型：
--
作者：
Andolfo I;Martone S;Rosato BE;Marra R;Gambale A;Forni GL;Pinto V;Göransson M;Papadopoulou V;Gavillet M;Elalfy M;Panarelli A;Tomaiuolo G;Iolascon A;Russo R
遗传性红细胞疾病包括一大组具有不同分子基础和表型的疾病。我们在这里分析了2018至2020年间转诊至医学遗传学单位的155名临床怀疑遗传性红细胞缺陷的患者的病例系列。所有病例都遵循了基于有针对性的下一代测序小组的诊断工作流程，该小组由86个导致遗传性红细胞缺陷的基因组成。我们获得了84%的受试患者的总诊断率。单基因遗传占69%(107/155)，多基因遗传占15%(23/155)。PIEZO1和SPTA1是突变最多的基因座。相应地，23例多位点遗传病患者中有16例表现为脱水遗传性口红/干细胞症和遗传性球形红细胞增多症的双重分子诊断。这些双重遗传病例具有完全的特征性，在临床上与遗传性球形红细胞增多症患者无法区分。此外，与脱水遗传性口腔细胞增多症和遗传性球形细胞增多症相比，他们的红细胞计数曲线突出了双重遗传患者的变化。我们的发现扩大了红细胞疾病的基因型谱，并表明在对这些患者进行分析和咨询时应考虑多基因座遗传。值得注意的是，基因测试对于诊断具有复杂遗传模式的患者至关重要。
Hereditary erythrocytes disorders include a large group of conditions with heterogeneous molecular bases and phenotypes. We analyzed here a case series of 155 consecutive patients with clinical suspicion of hereditary erythrocyte defects referred to the Medical Genetics Unit from 2018 to 2020. All of the cases followed a diagnostic workflow based on a targeted next-generation sequencing panel of 86 genes causative of hereditary red blood cell defects. We obtained an overall diagnostic yield of 84% of the tested patients. Monogenic inheritance was seen for 69% (107/155), and multi-locus inheritance for 15% (23/155). PIEZO1 and SPTA1 were the most mutated loci. Accordingly, 16/23 patients with multi-locus inheritance showed dual molecular diagnosis of dehydrated hereditary stomatocytosis/xerocytosis and hereditary spherocytosis. These dual inheritance cases were fully characterized and were clinically indistinguishable from patients with hereditary spherocytosis. Additionally, their ektacytometry curves highlighted alterations of dual inheritance patients compared to both dehydrated hereditary stomatocytosis and hereditary spherocytosis. Our findings expand the genotypic spectrum of red blood cell disorders and indicate that multi-locus inheritance should be considered for analysis and counseling of these patients. Of note, the genetic testing was crucial for diagnosis of patients with a complex mode of inheritance.
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影响因子：
10.1
作者：
Andolfo I;Martone S;Ribersani M;Bianchi S;Manna F;Genesio R;Gambale A;Pignataro P;Testi AM;Iolascon A;Russo R
通讯作者：
Russo R
影响因子：
2.3
作者：
Russo, Roberta;Langella, Concetta;Esposito, Maria Rosaria;Gambale, Antonella;Vitiello, Francesco;Vallefuoco, Fara;Ek, Torben;Yang, Elizabeth;Iolascon, Achille
通讯作者：
Iolascon, Achille
DOI：
10.1056/nejmoa1515792
发表时间：
2016-06-09
期刊：
The New England journal of medicine
影响因子：
--
作者：
Tarailo-Graovac M;Shyr C;Ross CJ;Horvath GA;Salvarinova R;Ye XC;Zhang LH;Bhavsar AP;Lee JJ;Drögemöller BI;Abdelsayed M;Alfadhel M;Armstrong L;Baumgartner MR;Burda P;Connolly MB;Cameron J;Demos M;Dewan T;Dionne J;Evans AM;Friedman JM;Garber I;Lewis S;Ling J;Mandal R;Mattman A;McKinnon M;Michoulas A;Metzger D;Ogunbayo OA;Rakic B;Rozmus J;Ruben P;Sayson B;Santra S;Schultz KR;Selby K;Shekel P;Sirrs S;Skrypnyk C;Superti-Furga A;Turvey SE;Van Allen MI;Wishart D;Wu J;Wu J;Zafeiriou D;Kluijtmans L;Wevers RA;Eydoux P;Lehman AM;Vallance H;Stockler-Ipsiroglu S;Sinclair G;Wasserman WW;van Karnebeek CD
通讯作者：
van Karnebeek CD
DOI：
10.1038/s41436-020-01026-4
发表时间：
2021-04
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1056/nejmoa1516767
发表时间：
2017-01-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Posey JE;Harel T;Liu P;Rosenfeld JA;James RA;Coban Akdemir ZH;Walkiewicz M;Bi W;Xiao R;Ding Y;Xia F;Beaudet AL;Muzny DM;Gibbs RA;Boerwinkle E;Eng CM;Sutton VR;Shaw CA;Plon SE;Yang Y;Lupski JR
通讯作者：
Lupski JR