A respiratory/Hirschsprung phenotype in a three‐generation family associated with a novel pathogenic PHOX2B splice donor mutation,Molecular Genetics & Genomic Medicine

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A respiratory/Hirschsprung phenotype in a three‐generation family associated with a novel pathogenic PHOX2B splice donor mutation
Molecular Genetics & Genomic Medicine ( IF 1.5 ) Pub Date : 2020-10-13 , DOI: 10.1002/mgg3.1528
Nikolai Paul Pace ₁ , Michael Pace Bardon ₂ , Isabella Borg _{1,

3,

4}

Affiliation

Mutations in the PHOX2B gene cause congenital central hypoventilation syndrome (CCHS), a rare autonomic nervous system dysfunction disorder characterized by a decreased ventilatory response to hypercapnia. Affected subjects develop alveolar hypoventilation requiring ventilatory support particularly during the non‐REM phase of sleep. In more severe cases, hypoventilation may extend into wakefulness. CCHS is associated with disorders characterized by the defective migration/differentiation of neural crest derivatives, including aganglionic megacolon or milder gastrointestinal phenotypes, such as constipation. Most cases of CCHS are de novo, caused by heterozygosity for polyalanine repeat expansion mutations (PARMs) in exon 3. About 10% of cases are due to heterozygous non‐PARM missense, nonsense or frameshift mutations.

中文翻译：

与新的致病性PHOX2B剪接供体突变相关的三代家庭的呼吸/ Hirschsprung表型

PHOX2B中的突变基因引起先天性中枢通气不足综合征（CCHS），这是一种罕见的自主神经系统功能障碍，其特征为对高碳酸血症的通气反应降低。受影响的受试者出现肺泡通气不足，需要通气支持，尤其是在非REM睡眠阶段。在更严重的情况下，换气不足可能会导致觉醒。CCHS与以神经c衍生物（包括神经节巨结肠或较温和的胃肠道表型，如便秘）缺陷的迁移/分化为特征的疾病有关。CCHS的大多数病例是从头开始的，是由外显子3的聚丙氨酸重复扩增突变（PARM）的杂合性引起的。大约10％的病例是由于杂合的非PARM错义，无义或移码突变引起的。

更新日期：2020-10-13

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