In:
Fetal Diagnosis and Therapy, S. Karger AG, Vol. 38, No. 4 ( 2015), p. 296-306
Abstract:
〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 To identify the molecular basis for prenatally suspected cases of megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) (MIM 249210) in 3 independent families with clinical and radiographic evidence of MMIHS. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Whole-exome sequencing (WES) and Sanger sequencing of the ACTG2 gene. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 We identified a novel heterozygous de novo missense variant in 〈 i 〉 ACTG2 〈 /i 〉 c.770G 〉 A (p.Arg257His) encoding & #947;-2 smooth muscle actin (ACTG2) in 2 siblings with MMIHS, suggesting gonadal mosaicism of one of the parents. Two additional de novo missense variants (p.Arg257Cys and p.Arg178His) in ACTG2 were identified in 2 additional MMHIS patients. All of our patients had evidence of fetal megacystis and a normal or slightly increased amniotic fluid volume. Additional findings included bilateral renal hydronephrosis, an enlarged fetal stomach, and transient dilated bowel loops. 〈 i 〉 ACTG2 〈 /i 〉 immunostaining of the intestinal tissue showed an altered muscularis propria, a markedly thinned longitudinal muscle layer, and a reduced amount and abnormal distribution of ACTG2. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Our study demonstrates that de novo mutations in 〈 i 〉 ACTG2 〈 /i 〉 are a cause of fetal megacystis in MMIHS and that gonadal mosaicism may be present in a subset of cases. These findings have implications for the counseling of families with a diagnosis of fetal megacystis with a preserved amniotic fluid volume and associated gastrointestinal findings.
Type of Medium:
Online Resource
ISSN:
1015-3837
,
1421-9964
Language:
English
Publisher:
S. Karger AG
Publication Date:
2015
detail.hit.zdb_id:
1482292-1