Novel TTC37 mutations in a patient with Trichohepatoenteric syndrome: a case report and literature review.
Novel TTC37 mutations in a patient with Trichohepatoenteric syndrome: a case report and literature review.
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DOI：
10.21037/tp-21-574
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发表时间：
2022-06
影响因子：
2
通讯作者：
中科院分区：
文献类型：
--
作者：
毛发肝肠综合征（THES）是一种罕见的常染色体隐性遗传病，由TTC 37或SKIV 2L基因突变引起。临床表现多种多样，包括顽固性腹泻、羊毛状毛发异常、免疫功能障碍、宫内生长受限（IUGR）、面部畸形，有时还有肝脏和皮肤异常。虽然在新加坡、中国台湾和马来西亚已经报道了4例患有THES综合征1的中国儿童，但据我们所知，这是中国大陆首次报道患有THES的患者，具有经典的血小板特征、临床病程和TTC 37基因的新突变。男婴有对称性IUGR，出生于37+1周，出生体重为1，480 g。他在新生儿重症监护室住院期间，从出生后第12天开始出现喂养困难和呕吐，从出生后第21天开始出现过度腹泻。从出生后第35天开始，即使是轻微低渗的口服补液溶液也会引起水样便。即使仅肠外输注葡萄糖速率高达14 mg/kg/min，血糖水平仍低于3.3 mmol/L，这在既往文献中未见报道。血小板中偶见正常α颗粒。全外显子组测序分析确定了TTC 37基因中的复合杂合突变（c.4130C > G：p.S1377X）和（Exon 11 -13 del），分别遗传自其父亲和母亲。据我们所知，上述突变尚未在任何数据库或以前的文献中描述。采用全胃肠外营养作为治疗的支柱，并使用氢化可的松（1 mg/kg/剂，每4小时一次）维持血糖水平。患者出院后最终预后不佳。该病例表现为轻度血小板异常和顽固性低血糖，扩展了已知的THES突变和表型。中国患者的临床特征与其他种族一致。分子诊断对不明原因的顽固性腹泻患者很有用，这结束了漫长的诊断之旅。
Trichohepatoenteric syndrome (THES) is a rare autosomal recessive genetic disease caused by pathogenic mutations in TTC37 or SKIV2L gene. The presentation is variable, including intractable diarrhea, woolly hair abnormality, immune dysfunction, intrauterine growth restriction (IUGR), facial dysmorphism, and sometimes liver and skin abnormalities. Although four Chinese children affected with THES syndrome 1 have been described in Singapore, Taiwan (China) and Malaysia, to our knowledge, this is the first report of a patient with THES in Mainland China, harboring classical platelets features, clinical course, and novel mutations in TTC37 gene. The male infant had symmetrical IUGR, and was born at 37+1 weeks with a birth weight of 1,480 g. He presented with feeding difficulties and vomiting from the 12th day after birth during the stay in neonatal intensive care unit, and had excessive diarrhea from the 21st day after birth. From the 35th day after birth, even slightly hypotonic oral rehydration solution caused watery stools. The blood glucose level was lower than 3.3 mmol/L even when the glucose infusion rate was up to 14 mg/kg/min on the parenteral alone, which has not been reported in previous literature. Normal α-granules were observed occasionally in THES platelets. Whole-exome sequencing analysis identified compound heterozygous mutations (c.4130C > G: p.S1377X) and (Exon11-13 del) in the TTC37 gene, which had been inherited from his father and mother, respectively. To our knowledge, the above mutations have not been described in any database or previous literature. Total parenteral nutrition was employed as mainstay of therapy, and hydrocortisone (1 mg/kg/dose, every 4 hours) was used to maintain blood glucose levels. The patient’s final prognosis was poor after discharged from the hospital. This case presented with mild platelet abnormality and intractable hypoglycemia, which extends the known mutation and phenotype of THES. The clinical features of Chinese patient are consistent with other ethnicity. Molecular diagnosis is useful for patients with unexplained intractable diarrhea, which puts an end to a long diagnostic odyssey.
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影响因子：
4.5
作者：
Kohda M;Tokuzawa Y;Kishita Y;Nyuzuki H;Moriyama Y;Mizuno Y;Hirata T;Yatsuka Y;Yamashita-Sugahara Y;Nakachi Y;Kato H;Okuda A;Tamaru S;Borna NN;Banshoya K;Aigaki T;Sato-Miyata Y;Ohnuma K;Suzuki T;Nagao A;Maehata H;Matsuda F;Higasa K;Nagasaki M;Yasuda J;Yamamoto M;Fushimi T;Shimura M;Kaiho-Ichimoto K;Harashima H;Yamazaki T;Mori M;Murayama K;Ohtake A;Okazaki Y
通讯作者：
Okazaki Y
影响因子：
7.3
作者：
Vély F;Barlogis V;Marinier E;Coste ME;Dubern B;Dugelay E;Lemale J;Martinez-Vinson C;Peretti N;Perry A;Bourgeois P;Badens C;Goulet O;Hugot JP;Farnarier C;Fabre A
通讯作者：
Fabre A
影响因子：
5.2
作者：
STANKLER, L;LLOYD, D;RUSSELL, G
通讯作者：
RUSSELL, G
靶向二代测序鉴定毛肝肠综合征患者 SKIV2L 基因的新型错义突变
影响因子：
3.4
作者：
Zheng, Bixia;Pan, Jian;Liu, Zhifeng
通讯作者：
Liu, Zhifeng
影响因子：
1.6
作者：
Lee WI;Huang JL;Chen CC;Lin JL;Wu RC;Jaing TH;Ou LS
通讯作者：
Ou LS