原发性纤毛运动障碍的新型致病DNAH5变异:与内脏异位和新生儿胆汁淤积有关。

IF 0.4 Q4 PEDIATRICS
Hong T Lin, Anita Gupta, Kevin E Bove, Sara Szabo, Fang Xu, Anthony Krentz, Amelle L Shillington
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引用次数: 0

摘要

动力蛋白轴突重链5基因编码一个轴突动力蛋白亚基,是纤毛运动功能所必需的。尽管研究已经阐明了该基因的一些变异的后果,但由于原发性纤毛运动障碍(PCD, Kartagener综合征是其中的一个子集)的罕见性,尚不清楚DNAH5位点的许多变异是良性的还是致病的。在这里,我们介绍一个男婴的病例,表现为典型的PCD,同时伴有内脏异位和新生儿胆汁淤积。基因检测表明该患者为复合杂合子,母源性等位基因c.8498G > a(称为致病性),父源性等位基因c.1206T > a和c.7800T > G两个意义不确定的变异。由于PCD是常染色体隐性遗传,我们得出结论,一个,或两个,这些父亲衍生的变异是致病的。据我们所知,这是第一次记录c.1206T > A (p.Asn402Lys)和c.7800T > G (p.Ile2600Met)的临床意义。此外,我们以这个病例为例,建议临床医生在出现严重的婴儿胆汁淤积时评估PCD和侧侧缺陷。虽然胆汁淤积与PCD的关联相对不常见,但PCD是胆道闭锁和感染患病率增加的危险因素,这两种情况都是婴儿早期胆汁淤积的已知原因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Novel Pathogenic DNAH5 Variants in Primary Ciliary Dyskinesia: Association with Visceral Heterotaxia and Neonatal Cholestasis.

The dynein axonemal heavy chain 5 gene codes for a subunit of axonemal dynein necessary for ciliary motor function. Though research has elucidated the consequences of some variants in this gene, it is still unclear whether many variants in the DNAH5 locus are benign or pathogenic due to the rarity of primary ciliary dyskinesia (PCD, of which Kartagener's syndrome is a subset). Here, we introduce the case of an infant boy presenting with the classical findings of PCD along with visceral heterotaxia and neonatal cholestasis. Genetic testing indicated that the patient is a compound heterozygote with a pathogenic c.8498G > A (known as pathogenic) on the maternally derived allele and two variants of uncertain significance, c.1206T > A and c.7800T > G, on the paternally derived allele. As PCD is autosomal recessive, we conclude that one, or both, of these paternally derived variants are pathogenic. To our knowledge, this is the first time that the clinical implications of c.1206T > A (p.Asn402Lys) and c.7800T > G (p.Ile2600Met) are documented. Furthermore, we use this case as an example to recommend clinicians to assess for PCD and laterality defects when presented with severe infantile cholestasis. While the association of cholestasis with PCD is relatively uncommon, PCD is a risk factor for increased prevalence of biliary atresia and infections, both of which are known causes of cholestasis in early infancy.

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来源期刊
自引率
0.00%
发文量
32
期刊介绍: The Journal of Pediatric Genetics is an English multidisciplinary peer-reviewed international journal publishing articles on all aspects of genetics in childhood and of the genetics of experimental models. These topics include clinical genetics, molecular genetics, biochemical genetics, medical genetics, dysmorphology, teratology, genetic counselling, genetic engineering, formal genetics, neuropsychiatric genetics, behavioral genetics, community genetics, cytogenetics, hereditary or syndromic cancer genetics, genetic mapping, reproductive genetics, fetal pathology and prenatal diagnosis, multiple congenital anomaly syndromes, and molecular embryology of birth defects. Journal of Pediatric Genetics provides an in-depth update on new subjects and current comprehensive coverage of the latest techniques used in the diagnosis of childhood genetics. Journal of Pediatric Genetics encourages submissions from all authors throughout the world. The following articles will be considered for publication: editorials, original and review articles, short report, rapid communications, case reports, letters to the editor, and book reviews. The aim of the journal is to share and disseminate knowledge between all disciplines in the field of pediatric genetics. This journal is a publication of the World Pediatric Society: http://www.worldpediatricsociety.org/ The Journal of Pediatric Genetics is available in print and online. Articles published ahead of print are available via the eFirst service on the Thieme E-Journals platform.
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