A novel heterotaxy gene: Expansion of the phenotype of TTC21B-spectrum disease.
A novel heterotaxy gene: Expansion of the phenotype of TTC21B-spectrum disease.
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DOI：
10.1002/ajmg.a.62093
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发表时间：
2021-04
影响因子：
2
通讯作者：
Hakonarson, Hakon
中科院分区：
文献类型：
--
作者：
Strong, Alanna;Li, Dong;Mentch, Frank;Hakonarson, Hakon
TTC21 B编码蛋白质IFFT 139，这是初级纤毛内逆行运输系统的关键组成部分。双等位基因致病性TTC21B变异体与经典的纤毛病综合征相关，包括肾单位营养不良、青窒息性胸营养不良和Joubert综合征，具有纤毛病谱系特征，如胆道发育不全、原发性纤毛运动障碍和逆位，还与局灶性节段性肾小球硬化症相关。我们报告了一名9岁男性，患有局灶节段性肾小球硬化症，需要肾移植，原发性纤毛运动障碍和胆道发育不全，通过基于研究的外显子组测序发现具有双等位基因致病性TTC21B变体。发现一个孤立性内脏异位的兄弟姐妹也有相同的变异。该病例突出了TTC21 B相关疾病的表型谱和不可预测的表现，并首次报告了TTC21 B与异位之间的关联，提名TTC21 B为重要的新异位基因。
TTC21B encodes the protein IFT139, a critical component of the retrograde transport system within the primary cilium. Biallelic, pathogenic TTC21B variants are associated with classic ciliopathy syndromes, including nephronophthisis, Jeune asphyxiating thoracic dystrophy, and Joubert Syndrome, with ciliopathy‐spectrum traits such as biliary dysgenesis, primary ciliary dyskinesia, and situs inversus, and also with focal segmental glomerulosclerosis. We report a 9‐year‐old male with focal segmental glomerulosclerosis requiring kidney transplant, primary ciliary dyskinesia, and biliary dysgenesis, found by research‐based exome sequencing to have biallelic pathogenic TTC21B variants. A sibling with isolated heterotaxy was found to harbor the same variants. This case highlights the phenotypic spectrum and unpredictable manifestations of TTC21B‐related disease, and also reports the first association between TTC21B and heterotaxy, nominating TTC21B as an important new heterotaxy gene.
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影响因子：
2
作者：
Strong, Alanna;Li, Dong;Mentch, Frank;Hakonarson, Hakon
通讯作者：
Hakonarson, Hakon
影响因子：
7.3
作者：
Gabriel GC;Young CB;Lo CW
通讯作者：
Lo CW
影响因子：
12.3
作者：
Shaheen R;Szymanska K;Basu B;Patel N;Ewida N;Faqeih E;Al Hashem A;Derar N;Alsharif H;Aldahmesh MA;Alazami AM;Hashem M;Ibrahim N;Abdulwahab FM;Sonbul R;Alkuraya H;Alnemer M;Al Tala S;Al-Husain M;Morsy H;Seidahmed MZ;Meriki N;Al-Owain M;AlShahwan S;Tabarki B;Salih MA;Ciliopathy WorkingGroup;Faquih T;El-Kalioby M;Ueffing M;Boldt K;Logan CV;Parry DA;Al Tassan N;Monies D;Megarbane A;Abouelhoda M;Halees A;Johnson CA;Alkuraya FS
通讯作者：
Alkuraya FS
影响因子：
3.9
作者：
Liu, Hui;Giguet-Valard, Anna-Gaelle;Bouvagnet, Patrice
通讯作者：
Bouvagnet, Patrice
影响因子：
13.6
作者：
Cong, Evelyne Huynh;Bizet, Albane A.;Antignac, Corinne
通讯作者：
Antignac, Corinne