当前位置: X-MOL 学术Pediatr. Devel. Pathol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Fetal Description of the Pancreatic Agenesis and Holoprosencephaly Syndrome Associated to a Specific CNOT1 Variant
Pediatric and Developmental Pathology ( IF 1.9 ) Pub Date : 2022-04-28 , DOI: 10.1177/10935266221095305
Auriane Cospain 1, 2 , Marie Faoucher 2, 3 , Aurélie Cauchois 4 , Wilfrid Carre 2, 3 , Chloé Quelin 1, 4 , Christèle Dubourg 2, 3
Affiliation  

Holoprosencephaly (HPE) is a clinically and genetically heterogeneous disease, which can be associated with various prenatal comorbidities not always detectable on prenatal ultrasound. We report on the case of a foetus carrying a semi-lobar HPE diagnosed at ultrasound, for which a fetal autopsy and a whole exome sequencing were performed following a medical termination of pregnancy. Neuropathological examination confirmed the semi-lobar HPE and general autopsy disclosed a total pancreas agenesis. Whole exome sequencing found the CNOT1 missense c.1603C>T, p.(Arg535Cys), occurring de novo in the foetus. The same variant was previously reported in 5 unrelated children. All individuals had HPE, and 4 out of 5 presented endo- and exocrine pancreatic insufficiency or total pancreas agenesis. CNOT1 encodes a subunit of the CCRN4-NOT complex, expressed at the early stage of embryonic development. This report is the first fetal description of the phenotype associating HPE and pancreatic agenesis linked to the recurrent CNOT1 missense c.1603C>T, p.(Arg535Cys). This finding strengthens the hypothesis of a specific recurrent variant associated with a particular phenotype of HPE and pancreas agenesis. The fetal autopsy that revealed the pancreas agenesis was crucial in guiding the genetic diagnosis and enabling accurate genetic counselling.



中文翻译:

与特定 CNOT1 变体相关的胰腺发育不全和全前脑综合征的胎儿描述

Holoprosencephaly (HPE) 是一种临床和遗传异质性疾病,它可能与各种产前合并症相关,但产前超声并不总是能检测到。我们报告了一个胎儿携带半叶HPE 超声诊断的病例,在医学终止妊娠后对其进行了胎儿尸检和全外显子组测序。神经病理学检查证实半叶HPE和一般尸检显示胰腺完全发育不全。全外显子组测序发现CNOT1错义 c.1603C>T, p.(Arg535Cys),从头发生在胎儿中。先前在 5 名无关儿童中报告了相同的变体。所有个体都有 HPE,5 人中有 4 人出现胰腺内外分泌功能不全或全胰腺发育不全。CNOT1编码 CCRN4-NOT 复合体的一个亚基,在胚胎发育的早期阶段表达。该报告是对与复发性CNOT1错义 c.1603C>T, p.(Arg535Cys)相关的 HPE 和胰腺发育不全的表型的第一次胎儿描述。这一发现加强了与 HPE 和胰腺发育不全的特定表型相关的特定复发变异的假设。揭示胰腺发育不全的胎儿尸检对于指导基因诊断和实现准确的遗传咨询至关重要。

更新日期:2022-04-28
down
wechat
bug