平滑肌运动障碍表型：与七个致病基因相关的病例的系统评价（ ACTG2 ， MYH11 ， FLNA ，MYLK,RAD21 、 MYL9 和 LMOD1) 。Smooth muscle motility disorder phenotypes: A systematic review of cases associated with seven pathogenic genes (ACTG2, MYH11, FLNA, MYLK, RAD21, MYL9 and LMOD1).-医云文献数字医云科研云海量医学决策数据服务

Abstract：

Smooth muscle disorders affecting both the intestine and the bladder have been known for a decade. However, the recent discovery of genes associated with these dysfunctions has led to the description of several clinical phenotypes. We performed a systematic review of all published cases involving seven genes with pathogenic variants, ACTG2, MYH11, FLNA, MYLK, RAD21, MYL9 and LMOD1, and included 28 articles describing 112 patients and 5 pregnancies terminated before birth. The most commonly described mutations involved ACTG2 (75/112, 67% of patients), MYH11 (14%) and FLNA (13%). Twenty-seven patients (28%) died at a median age of 14.5 months. Among the 76 patients for whom this information was available, 10 (13%) had isolated chronic intestinal pseudo-obstruction (CIPO), 17 (22%) had isolated megacystis, and 48 (63%) had combined CIPO and megacystis. The respective proportions of these phenotypes were 9%, 20% and 71% among the 56 patients with ACTG2 mutations, 20%, 20% and 60% among the 10 patients with MYH11 mutations and 50%, 50% and 0% among the 7 patients with FLNA mutations.

摘要：

影响肠道和膀胱的平滑肌疾病已经知道了十年。然而,最近发现的与这些功能障碍相关的基因导致了几种临床表型的描述。我们对所有已发表的病例进行了系统评价，涉及7种具有致病变异的基因，ACTG2,MYH11,FLNA,MYLK,RAD21，MYL9和LMOD1，包括28篇文章，描述了112例患者和5例出生前终止妊娠。最常见的突变涉及ACTG2（75/112，67%的患者），MYH11（14%）和FLNA（13%）。27名患者（28％）的中位年龄为14.5个月。在76名患者中，这些信息是可用的，10例（13%）患有孤立性慢性假性肠梗阻（CIPO），17人(22%)曾隔离过巨型猪，48人(63%)患有合并的CIPO和巨细胞病。这些表型的比例分别为9%，在56例ACTG2突变患者中，有20%和71%，20%,10例MYH11突变患者中20%和60%,50%,7例患者中存在FLNA突变的分别为50%和0%。

Smooth muscle motility disorder phenotypes: A systematic review of cases associated with seven pathogenic genes (ACTG2, MYH11, FLNA, MYLK, RAD21, MYL9 and LMOD1).

1 Megacystis microcolon intestinal hypoperistalsis syndrome: systematic review of outcome.

2 Prune belly syndrome in surviving males can be caused by Hemizygous missense mutations in the X-linked Filamin A gene.

3 Pediatric Intestinal Pseudo-obstruction in the Era of Genetic Sequencing.

4 Differential regulation of two FLNA transcripts explains some of the phenotypic heterogeneity in the loss-of-function filaminopathies.

5 Megacystis Microcolon Intestinal Hypoperistalsis Syndrome in Which a Different De Novo Actg2 Gene Mutation was Detected: A Case Report.

6 Exon skipping causes atypical phenotypes associated with a loss-of-function mutation in FLNA by restoring its protein function.

7 16p13.11 microdeletion uncovers loss-of-function of a MYH11 missense variant in a patient with megacystis-microcolon-intestinal-hypoperistalsis syndrome.

8 Homozygous deletion in MYL9 expands the molecular basis of megacystis-microcolon-intestinal hypoperistalsis syndrome.

9 New Insights into the Genetics of Fetal Megacystis: ACTG2 Mutations, Encoding γ-2 Smooth Muscle Actin in Megacystis Microcolon Intestinal Hypoperistalsis Syndrome (Berdon Syndrome).

10 Mutation in Actin γ-2 Responsible for Megacystis Microcolon Intestinal Hypoperistalsis Syndrome in 4 Chinese Patients.

11 Megacystis microcolon intestinal hypoperistalsis syndrome.

12 Megacystis-microcolon-intestinal hypoperistalsis syndrome: case report and review of prenatal ultrasonographic findings.

13 Compound heterozygous variants in MYH11 underlie autosomal recessive megacystis-microcolon-intestinal hypoperistalsis syndrome in a Chinese family.

14 Megacystis-microcolon-intestinal hypoperistalsis syndrome: a new cause of intestinal obstruction in the newborn. Report of radiologic findings in five newborn girls.

15 Megacystis microcolon intestinal hypoperistalsis syndrome: Case series and updated review of the literature with an emphasis on urologic management.

16 Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections.

17 Protein-elongating mutations in MYH11 are implicated in a dominantly inherited smooth muscle dysmotility syndrome with severe esophageal, gastric, and intestinal disease.

18 Paediatric Intestinal Pseudo-obstruction: Evidence and Consensus-based Recommendations From an ESPGHAN-Led Expert Group.

19 Variants in ACTG2 underlie a substantial number of Australasian patients with primary chronic intestinal pseudo-obstruction.

20 Diagnosis of Chronic Intestinal Pseudo-obstruction and Megacystis by Sequencing the ACTG2 Gene.

21 Megacystis microcolon intestinal hypoperistalsis syndrome: bladder distension and pyelectasis in the fetus without anatomic outflow obstruction.

22 A Novel Mutation in ACTG2 Gene in Mother with Chronic Intestinal Pseudoobstruction and Fetus with Megacystis Microcolon Intestinal Hypoperistalsis Syndrome.

23 Heterozygous de novo and inherited mutations in the smooth muscle actin (ACTG2) gene underlie megacystis-microcolon-intestinal hypoperistalsis syndrome.

24 Chronic Intestinal Pseudo-obstruction.

25 Identification of a dominant MYH11 causal variant in chronic intestinal pseudo-obstruction: Results of whole-exome sequencing.

26 Megacystis microcolon intestinal hypoperistalsis syndrome: A report of a nationwide survey in Japan.

27 Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice.

28 Prenatal diagnosis of chronic intestinal pseudo-obstruction and paternal somatic mosaicism for the ACTG2 pathogenic variant.

29 ACTG2 variants impair actin polymerization in sporadic Megacystis Microcolon Intestinal Hypoperistalsis Syndrome.

30 Mutations in RAD21 disrupt regulation of APOB in patients with chronic intestinal pseudo-obstruction.

31 Loss-of-Function Variants in MYLK Cause Recessive Megacystis Microcolon Intestinal Hypoperistalsis Syndrome.

32 Variants of the ACTG2 gene correlate with degree of severity and presence of megacystis in chronic intestinal pseudo-obstruction.

33 De novo ACTG2 mutations cause congenital distended bladder, microcolon, and intestinal hypoperistalsis.

34 Recurrent arginine substitutions in the ACTG2 gene are the primary driver of disease burden and severity in visceral myopathy.

35 Phenotypic expansion of visceral myopathy associated with ACTG2 tandem base substitution.

36 ACTG2-Associated Visceral Myopathy With Chronic Intestinal Pseudoobstruction, Intestinal Malrotation, Hypertrophic Pyloric Stenosis, Choledochal Cyst, and a Novel Missense Mutation.

37 Visceral myopathy: Clinical and molecular survey of a cohort of seven new patients and state of the art of overlapping phenotypes.