PIGN mutation multiple congenital anomalies-hypotonia-seizures syndrome 1: A case report

INTRODUCTION

Multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1) associated with mutations ingene, is an autosomal recessive disease featured as epilepsy, stunting, hypotonica, and various congenital disorders. This was initially described in 2011[1]. Mutation in thegene involved in GPI-anchor pathway have been identified cause varied neurological abnormalities[1-4].The authors report on a 16 years old girl who was presented with epilepsy, developmental delay and cerebellar atrophy. She harbors a compound heterozygous variant in thegene, include a nonsense splice site mutation (c.2557A>C) which was inherited from her mother, and a novel site mutation (c.980del) which was inherited from her father.

CASE PRESENTATION

Chief complaints

A female, 16 years old, was presented with epilepsy, developmental delay and cerebellar atrophy.

History of present illness

Clinical examination documented the eyes were deep set with nystagmus, a small nose with nasalbridge (Figure 1).

The authors will keep on to follow the patient’s disease development. This diagnosis allowed permitted appropriate genetic counseling with related risk evaluation.

History of past illness

柬埔寨留學(xué)生和本土學(xué)生漢語學(xué)習(xí)的目標(biāo)需求對比研究…………………………………………………王睿昕（123）

Personal and family history

The patient was the second child of the family (non-consanguineous), her mother was 33 years old. She was born at full term with normal birth parameters, the pregnancy was normal, there was no known teratogenic exposure.

The parents does not have a personal history of seizures, nor is there a family history seizures.

Physical examination

Weakness of muscles was noticed at age 2 years old. At 1 year of age, she developed clinical seizures. Her seizure types include twitching movements, starting episodes, cluster seizures, and spasms. At a year and a half, there was only partial response to anti-convulsive therapy. Subsequently, global developmental delay was noted by 2 years old of age, there was no speech, and she needed assistance with daily life activities.

Laboratory examinations

Whole exome sequencing (WES) was performed commercially at Berrygenomics on the patient and her parents. Sequencing was performed on Illumina Novaseq 6000 (Illumina, San Diego, United States), using the Nano WES Human Exome V1.0 (Berrygenomics, Beijing, China) kit with 200 bp paired-end read, according to the manufacturer’s instructions. Annotation of variants was performed using GATK (https://software.broadinstitute.org/gatk/), gnomAD (http://gnomad.broadinstitute.org/), 1000genomes (http://browser.1000genomes.org), SIFT (http://sift.jcvi.org), FATHMM (http://fathmm.biocompute.org.uk), MutationAssessor (http://mutationassessor.org), OMIM (http://www.omim.org), ClinVar (http://www.ncbi.nlm.nih.gov/clinvar), HGMD (http:// www.hgmd.org).

Sanger sequening

出露的地層主要有泥盆系上統(tǒng)安格爾音烏拉組、石炭系上統(tǒng)寶力高廟組，白堊系下統(tǒng)白音高老組、梅勒圖組，以及新近系上新統(tǒng)寶格達(dá)烏拉組。（1）安格爾音烏拉組（D3a）為一套淺變質(zhì)沉積地層，巖性為灰綠色粉砂質(zhì)板巖；（2）寶力高廟組（C2bl）為一套淺變質(zhì)的火山巖，主要巖性為安山質(zhì)角礫凝灰?guī)r、安山巖等，是礦區(qū)的主要含礦層位；（3）白音高老組（K1b）為一套酸性火山巖，主要巖性為流紋質(zhì)玻屑凝灰?guī)r、流紋質(zhì)熔結(jié)凝灰?guī)r、石泡流紋巖等；（4）梅勒圖組（K1m）主要巖性為安山玄武巖；（5）寶格達(dá)烏拉組（N2b）主要巖性為棕褐色泥巖、泥質(zhì)砂巖等，分布于草原地勢低平處。

Imaging examinations

Neuropsychological testing demonstrated moderate intellectual disability. Brain imaging showed the progression of mild global cerebral volume loss and cerebellar atrophy. The parents could not provide the results of previous test, including brain magnetic resonance imaging, various metabolic tests.

首先，電力公司要抓好電力生產(chǎn)的安全管理動態(tài)評價，落實各級生產(chǎn)部門的安全職責(zé)。要從各個方面對電力系統(tǒng)安全生產(chǎn)過程進(jìn)行監(jiān)督，根據(jù)實際情況完善生產(chǎn)管理的監(jiān)督體制，要確立行政責(zé)任制度，明確各個部門的第一負(fù)責(zé)人。按照電力公司的安全生產(chǎn)計劃表，將供電線路和電力設(shè)備進(jìn)行逐級分配，將責(zé)任嚴(yán)格落實到個人。此外，各級安全監(jiān)督負(fù)責(zé)人還要做好電力安全生產(chǎn)事故的匯報和總結(jié)工作，舉一反三，深刻吸取事故中的經(jīng)驗和教訓(xùn)。電力公司還要組織工作人員進(jìn)行安全工作的教育和培訓(xùn)，例舉出一些典型的安全事故，提高員工安全生產(chǎn)的意識。還要建立公司內(nèi)部電力系統(tǒng)安全生產(chǎn)事故責(zé)任制度，對已發(fā)生或者未遂事故的負(fù)責(zé)人進(jìn)行確定。

FINAL DIAGNOSIS

Whole Exome sequencing was performed commercially at BerryGenomics on the patient and her parents. Compound heterozygous mutations ingene were found, maternally inherited c.2557A>C and paternally inherited c.980del. The mutations were validated by sanger sequencing in the patient and her parents (Figure 2).

The authors also examined several small insertion/deletion variants (Indels), but none of these had an apparent connection to the clinical phenotype.

TREATMENT

The present therapies for patients withgene associated illnesses are mainly supportive, which were aimed to reduce the development of epileptic seizures.

OUTCOME AND FOLLOW-UP

改革開放以來，中國找鉀工作有了很大發(fā)展。進(jìn)入1985年，為了迅速改變中國嚴(yán)重缺鉀狀況，地質(zhì)部專門安排了中國柴達(dá)木盆地西部和北部鉀鹽的普查項目，為日后鉀鹽資源的重大發(fā)現(xiàn)，打下了堅實基礎(chǔ)。在國家政策指引和各項科研資金支持下，國投新疆羅布泊鉀鹽有限責(zé)任公司研發(fā)的“含鉀硫酸鎂亞型鹵水制取硫酸鉀”工藝 ，在新疆羅布泊鹽湖建成120萬噸/年硫酸鉀成套裝置，使我國擁有了世界領(lǐng)先的利用硫酸鹽型鹵水制取硫酸鉀的技術(shù)和產(chǎn)能世界第一的硫酸鉀大型裝置，該項目獲得2013年國家科技進(jìn)步一等獎。

通過計算得到在邊坡開挖后，其安全系數(shù)為Fs=1.052<1.25，破壞概率PL1為25.02%，可靠性指數(shù)為0.663(見圖5)，不滿足規(guī)范要求，故邊坡需進(jìn)行整體加固處理。

DISCUSSION

There are more than 20 genes that participated in GPI-anchor biosynthesis pathway.is responsible for supplement of phosphoethanolamine to the primary mannose in GPI[2]. Mutations in thegene involved in GPI biosynthesis, have been identified associated with MCAHS1[1,5,6]. The authors report a patient with epilepsy, global delay, cerebellar atrophy with amutation. The maternally inherited variant (c.2557A>C) has not been seen observed in the gnomAD and 1000genomes, which was called variants of unknown significance. The original mutation c.980del (paternally inherited) discovered in the prohand was estimated as “probably damaging”. The novel mutation changes the gene’s open reading frameshift, support the conclusion that the novel mutation detected in the patient cause major damage to the GPI-anchored protein, finally leading to the disorder.

Unlike previous reports[1,5,6], the patient did not have other visceral congenital anomalies of urinary, cardiac or gastrointestinal systems. Gastro-esophageal reflux, diaphragmatic hernia, brachycephaly, flat face, hypoplasia of distal parts of all fingers, open mouth, drooling have not been seen in the patient. Evaluation for mutations incausingassociated epilepsy or MCAHS1 should be considered in patients of all ethnicities with epilepsy. These phenotypic differences may be explained as allele specific effects.

Sequence analysis of exon 28 and 12 ofusing genomic DNA from the patient and her parents were performed by amplification of a 438 bp and 239 bp fragment containing the putative mutation identifiedexome sequencing. The sense primer sequence was 5’-TAAGTCAGTTTCATCACCGTTCTAT-3’ and the antisense primer sequence was 5’-ATTTCCTCTAATGACAAGCAACAC-3’ for exon 28. The sense primer sequence was 5’-TCTAGCAAATGACACTTTTAGAGA-3’, and the antisense primer sequence was 5’-TTCCTTACCACTGAGTTAAGAGG-3’ for exon 12.

The clinical severity of the disease seems to correlate with the predicted functional severity of the mutations seen in[6]. Depending upon the severity of mutations, major congenial anomalies may also be present. Other hypotheses of environmental and genetic modification need to be considered. It should also be noted here that for PIGN gene-associated with disability, some tissues are more sensitive than others during body development.

CONCLUSION

This case report expands the mutation spectrum found ingene, and strengthens the association betweenmutation and MCAHS1. Mutations ingene may be an underestimated cause of epilepsy. The authors recommend that, for patients with epilepsy or prenatal diagnosis of highly suspicious fetus, gene sequencing should be the preferred detection method.

She was vigorous in the newborn period and passed her newborn disease screening, began walking around the age of 18 mo.

ACKNOWLEDGEMENTS

The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).

FOOTNOTES

Hou F performed the research and wrote the manuscript; Shan S analyzed the data; Jin H designed the research study; all authors have read and approve the final manuscript.

The patient and her legal guardian, provided informed written consent prior to study enrollment.

The authors declare that they have no conflict of interest.

當(dāng)變壓器處于理想的狀態(tài)下，會得出變壓器的參數(shù)的關(guān)系為：當(dāng)空間參數(shù)處于運(yùn)行的狀態(tài)時候，將其劃定為一次繞組的接電源和二次繞組的開路的狀態(tài)。此外變壓器在受到電壓的UI作用下在一次繞組的N1內(nèi)所通過的電流I0將其稱之為空載電流。此外I0能夠產(chǎn)生磁通，可將其稱之為勵磁電流。在它的作用下，其中的二次繞組N2的兩端會感應(yīng)出電動的實例，可將變壓器的變換關(guān)系式為：

Authors are grateful to the patients and their families for their collaboration. The laboratory examination and data analysis were conducted in BerryGenomics.

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BYNC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is noncommercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

我國城市人口逐年遞增，導(dǎo)致排放污水的數(shù)量越來越多。以往的城市排水系統(tǒng)，大部分都是將污水直接排放到道路的兩邊或周圍的河流里，對城市環(huán)境造成了威脅，若依舊使用這種直接排放污水的方法，將會帶來嚴(yán)重的危害。因此，需確保城市排水的有效進(jìn)行，加大對排水系統(tǒng)的研究工作。在設(shè)計排水系統(tǒng)時，為防止因污水?dāng)?shù)量過于龐大導(dǎo)致污水不能順利地經(jīng)管道排出，從而對市民的生活造成影響，需要計算污水排放量。在排放污水時，還應(yīng)使用節(jié)能方式進(jìn)行排水，不斷加大污水的處理力度，同時也要提高對節(jié)能的重視程度。

China

發(fā)揚(yáng)風(fēng)格也不是隨意發(fā)揮，上文所提到的兩位翻譯家，魯迅和周作人，他們都認(rèn)為兒童文學(xué)翻譯作品的目標(biāo)讀者是兒童，因此應(yīng)該著重考慮兒童的閱讀習(xí)慣和心理。原文中一些晦澀難懂的詞匯應(yīng)該改成簡單生動的詞匯，所以在翻譯這些作品時，譯者要做二次創(chuàng)作。(夏丐尊，1983)[9]

Fei Hou 0000-0001-7164-9200; Shan Shan 0000-0002-8267-2833; Hua Jin 0000-0001-8008-8257.

從回歸系數(shù)t的數(shù)值來看，出口的對外直接投資彈性系數(shù)顯著.浙江省對外直接投資與出口之間存在著互補(bǔ)效應(yīng)，對外直接投資每增加1個百分點，浙江省的出口將會增加0.1個百分點.一個可能的解釋是：一方面，對外直接投資的增加，使得浙江省與東道國的貿(mào)易聯(lián)系增加，從而有助于出口的增加；另一方面，浙江省對外直接投資一旦進(jìn)入生產(chǎn)階段，則促進(jìn)了中間品、原材料和技術(shù)的出口.同時根據(jù)式(5)還可以看出，距離與貿(mào)易量呈顯著的負(fù)相關(guān)性，表明地理位置會影響兩個國家或地區(qū)的貿(mào)易往來，而且是重要影響因素.此外，樣本國與浙江省是否擁有共同邊界或者同屬于一個貿(mào)易集團(tuán)，對出口、進(jìn)口貿(mào)易的影響比較小或者不明顯.

Liu JH

A

Liu JH