Whole-Exome Sequencing Identified Novel CLMP Mutations in a Family With Congenital Short Bowel Syndrome Presenting Differently in Two Probands.

Yao-Hung Chuang,Kung-Hao Liang,Yu-De Chu,Ming-Wei Lai,Chien-Chang Chen,Wen-Lang Fan,Yuan-Ming Yeh,Cheng-Hsun Chiu

doi:10.3389/fgene.2020.574943

Abstract

Congenital short bowel syndrome (CSBS) is a rare condition characterized by an inborn shortening of bowel length with loss of intestinal functions, which often combines malrotation. CXADR-like membrane protein (CLMP) and filamin A (FLNA) gene mutations are the two major causes of this inherited defect. We presented two siblings with the older brother suffering from a laparotomy for bowel obstruction due to malrotation on the 17th day after birth. The younger sister encountered a laparotomy for lactobezoar at 6 months old. CSBS was diagnosed by measurement of the bowel length during the operations. Compound heterozygous CLMP mutations with the paternal allele harboring a long deletion across exon 3–5 and the maternal allele bearing a non-sense mutation of exon 3 (c.235C > T, p.Q79∗) were identified in both cases. They are the first reported familial CSBS caused by novel CLMP mutations in Taiwan.

Highlights

Congenital short bowel syndrome (CSBS) is a rare condition described first in 1969 by Hamilton (Hamilton et al, 1969)
Whole-exome sequencing (WES) was performed for all, and whole-genome sequencing (WGS) was conducted for one member in the family to search for potential causative genetic defect(s) of CSBS
Further validation using PCR followed by gel electrophoresis agreed with this finding as the deletion product, with a size of 4227 bp, was only detected in samples from the father and both children but not from the mother’s, which generated a full-length (7391 bp) fragment (Figure 3D)

Summary

Introduction

Congenital short bowel syndrome (CSBS) is a rare condition described first in 1969 by Hamilton (Hamilton et al, 1969). The prevalence of CSBS is less than 1/1,000,000 (Orphanet.). Defective neurenteric development, and myenteric plexus abnormalities could lead to such an intestinal defect (Tanner et al, 1976; Sansaricq et al, 1984). The diagnosis is often established at laparotomy exploration for intestinal obstruction in neonates or young infants because of nonspecific presentations. Malnutrition and diarrhea are two other main features in CSBS resulted from. Familial Congenital Short Bowel Syndrome the loss of small bowel length. CSBS was disclosed during operation in both. Whole-exome sequencing (WES) was performed for all, and whole-genome sequencing (WGS) was conducted for one member in the family to search for potential causative genetic defect(s) of CSBS

Methods

Results

Discussion

Conclusion