Hyper-IgE Syndrome due to an Elusive Novel Intronic Homozygous Variant in DOCK8.
Hyper-IgE Syndrome due to an Elusive Novel Intronic Homozygous Variant in DOCK8.
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DOI：
10.1007/s10875-021-01152-x
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发表时间：
2022-01
影响因子：
9.1
通讯作者：
Ma, Cindy S.
中科院分区：
文献类型：
--
作者：
Tangye, Stuart G.;Gray, Paul E.;Pillay, Bethany A.;Yap, Jin Yan;Figgett, William A.;Reeves, John;Kummerfeld, Sarah K.;Stoddard, Jennifer;Uzel, Gulbu;Jing, Huie;Su, Helen C.;Campbell, Dianne E.;Sullivan, Anna;Burnett, Leslie;Peake, Jane;Ma, Cindy S.
Rare, biallelic loss-of-function mutations in DOCK8 result in a combined immune deficiency characterized by severe and recurrent cutaneous infections, eczema, allergies, and susceptibility to malignancy, as well as impaired humoral and cellular immunity and hyper-IgE. The advent of next-generation sequencing technologies has enabled the rapid molecular diagnosis of rare monogenic diseases, including inborn errors of immunity. These advances have resulted in implementation of gene-guided treatments, such as hematopoietic stem cell transplant for DOCK8 deficiency. However, putative disease-causing variants revealed by next-generation sequencing need rigorous validation to demonstrate pathogenicity. Here, we report the eventual diagnosis of DOCK8 deficiency in a consanguineous family due to a novel homozygous intronic deletion variant that caused aberrant exon splicing and subsequent loss-of expression of DOCK8 protein. Remarkably, the causative variant was not initially detected by clinical whole genome sequencing, but was subsequently identified and validated by combining advanced genomic analysis, RNA-Seq and flow cytometry. This case highlights the need to adopt multi-pronged confirmatory approaches to definitively solve complex genetic cases that result from variants outside protein-coding exons and conventional splice sites.
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影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
DOI：
10.1084/jem.20180010
发表时间：
2018-08-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Avery DT;Kane A;Nguyen T;Lau A;Nguyen A;Lenthall H;Payne K;Shi W;Brigden H;French E;Bier J;Hermes JR;Zahra D;Sewell WA;Butt D;Elliott M;Boztug K;Meyts I;Choo S;Hsu P;Wong M;Berglund LJ;Gray P;O'Sullivan M;Cole T;Holland SM;Ma CS;Burkhart C;Corcoran LM;Phan TG;Brink R;Uzel G;Deenick EK;Tangye SG
通讯作者：
Tangye SG
影响因子：
14.9
作者：
Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
通讯作者：
Flicek P
DOI：
10.1016/j.jaci.2014.12.1945
发表时间：
2015-08
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Engelhardt KR;Gertz ME;Keles S;Schäffer AA;Sigmund EC;Glocker C;Saghafi S;Pourpak Z;Ceja R;Sassi A;Graham LE;Massaad MJ;Mellouli F;Ben-Mustapha I;Khemiri M;Kilic SS;Etzioni A;Freeman AF;Thiel J;Schulze I;Al-Herz W;Metin A;Sanal Ö;Tezcan I;Yeganeh M;Niehues T;Dueckers G;Weinspach S;Patiroglu T;Unal E;Dasouki M;Yilmaz M;Genel F;Aytekin C;Kutukculer N;Somer A;Kilic M;Reisli I;Camcioglu Y;Gennery AR;Cant AJ;Jones A;Gaspar BH;Arkwright PD;Pietrogrande MC;Baz Z;Al-Tamemi S;Lougaris V;Lefranc G;Megarbane A;Boutros J;Galal N;Bejaoui M;Barbouche MR;Geha RS;Chatila TA;Grimbacher B
通讯作者：
Grimbacher B
影响因子：
14.2
作者：
Al-Herz, Waleed;Chu, Julia I.;Pai, Sung-Yun
通讯作者：
Pai, Sung-Yun