A novel mutation in SEPN1 causing rigid spine muscular dystrophy 1: A Case report

Abstract Background Muscular dystrophies are a clinically and genetically heterogeneous group of disorders characterized by variable degrees of progressive muscle degeneration and weakness. There is a wide variability in the age of onset, symptoms and rate of progression in subtypes of these disorders. Herein, we present the results of our study conducted to identify the pathogenic genetic variation involved in our patient affected by rigid spine muscular dystrophy. Case presentation A 14-year-old boy, product of a first-cousin marriage, was enrolled in our study with failure to thrive, fatigue, muscular dystrophy, generalized muscular atrophy, kyphoscoliosis, and flexion contracture of the knees and elbows. Whole-exome sequencing (WES) was carried out on the DNA of the patient to investigate all coding regions and uncovered a novel, homozygous missense mutation in SEPN1 gene (c. 1379 C > T, p.Ser460Phe). This mutation has not been reported before in different public variant databases and also our database (BayanGene), so it is classified as a variation of unknown significance (VUS). Subsequently, it was confirmed that the novel variation was homozygous in our patient and heterozygous in his parents. Different bioinformatics tools showed the damaging effects of the variant on protein. Multiple sequence alignment using BLASTP on ExPASy and WebLogo, revealed the conservation of the mutated residue. Conclusion We reported a novel homozygous mutation in SEPN1 gene that expands our understanding of rigid spine muscular dystrophy. Although bioinformatics analyses of results were in favor of the pathogenicity of the mutation, functional studies are needed to establish the pathogenicity of the variant

Postoperative complications after procedure for prolapsed hemorrhoids (PPH) and stapled transanal rectal resection (STARR) procedures

Procedure for prolapsing hemorrhoids (PPH) and stapled transanal rectal resection for obstructed defecation (STARR) carry low postoperative pain, but may be followed by unusual and severe postoperative complications. This review deals with the pathogenesis, prevention and treatment of adverse events that may occasionally be life threatening. PPH and STARR carry the expected morbidity following anorectal surgery, such as bleeding, strictures and fecal incontinence. Complications that are particular to these stapled procedures are rectovaginal fistula, chronic proctalgia, total rectal obliteration, rectal wall hematoma and perforation with pelvic sepsis often requiring a diverting stoma. A higher complication rate and worse results are expected after PPH for fourth-degree piles. Enterocele and anismus are contraindications to PPH and STARR and both operations should be used with caution in patients with weak sphincters. In conclusion, complications after PPH and STARR are not infrequent and may be difficult to manage. However, if performed in selected cases by skilled specialists aware of the risks and associated diseases, some complications may be prevented

Truncating Mutations in UBAP1 Cause Hereditary Spastic Paraplegia

The diagnostic gap for rare neurodegenerative diseases is still considerable, despite continuous advances in gene identification. Many novel Mendelian genes have only been identified in a few families worldwide. Here we report the identification of an autosomal-dominant gene for hereditary spastic paraplegia (HSP) in 10 families that are of diverse geographic origin and whose affected members all carry unique truncating changes in a circumscript region of UBAP1 (ubiquitin-associated protein 1). HSP is a neurodegenerative disease characterized by progressive lower-limb spasticity and weakness, as well as frequent bladder dysfunction. At least 40% of affected persons are currently undiagnosed after exome sequencing. We identified pathological truncating variants in UBAP1 in affected persons from Iran, USA, Germany, Canada, Spain, and Bulgarian Roma. The genetic support ranges from linkage in the largest family (LOD = 8.3) to three confirmed de novo mutations. We show that mRNA in the fibroblasts of affected individuals escapes nonsense-mediated decay and thus leads to the expression of truncated proteins; in addition, concentrations of the full-length protein are reduced in comparison to those in controls. This suggests either a dominant-negative effect or haploinsufficiency. UBAP1 links endosomal trafficking to the ubiquitination machinery pathways that have been previously implicated in HSPs, and UBAP1 provides a bridge toward a more unified pathophysiology

Emerging technologies in coloproctology: results of the Italian Society of Colorectal Surgery Logbook of Adverse Events.

Background: The aim of this paper is to present the results of the Italian Society of Colorectal Surgery [or Società Italiana di Chirurgia Colorettale (SICCR)] Logbook of adverse events (AE) occurring in relation to emerging technologies in coloproctology (ETCs), over a 3-year period. METHODS: A total of 245 AE were reported (patients age: mean = 49.6 years, range = 20-75 years; gender: 155 = F, 90 = M). The "observations" originated from the same institution of the AEs in 44 cases (18.0%), while 201 patients (82.0%) had been operated on somewhere else. RESULTS: The three most reported ETCs were: Procedure for prolapsed haemorrhoids (PPH) (n = 120-48.9%), stapled transanal rectal resection (STARR (n = 96-39.2%), and transanal haemorrhoidal dearterialization (THD) (n = 11-4.5%). PPH, STARR, and THD together accounted for n = 227 (92.6%) observations. For the three main reported ETCs, the various AEs are listed. Chronic pain after PPH was 46/120 (38.3%), and after STARR of 21/96 (21.9%). The overall re-operation rate was n = 135 (55.1%) versus n = 110 (44.9%) no reoperation. In particular, for the three main reported ETCs, n = 68/120 (56.7%) following an AE after PPH, n = 47/94 (50.0%) following an AE after STARR, and n = 6/11 (54.5) following an AE post-THD. The various types of treatment to solve AE after each of the three most observed ETCs are reported in the text. CONCLUSIONS: Our results do not allow us to draw statistical conclusions; however, this was not the aim of our survey. ETCs are important, yet they are not without major risks. Manufacturers should help colorectal surgeons to convey the right message to patients

Erratum: Truncating Mutations in UBAP1 Cause Hereditary Spastic Paraplegia (The American Journal of Human Genetics (2019) 104(4) (767–773), (S0002929719300977), (10.1016/j.ajhg.2019.03.001))

(The American Journal of Human Genetics 104, 767–773; April 4, 2019) In the originally published version of this article, authors Ivailo Tournev and Teodora Chamova were mistakenly omitted from the author list. Their names have been added here. The online version of the full article now appears correctly and includes affiliations for the added authors as well as corrections to some of the other affiliations. The authors regret these omissions

Truncating mutations in UBAP1 cause hereditary spastic paraplegia

The diagnostic gap for rare neurodegenerative diseases is still considerable, despite continuous advances in gene identification. Many novel Mendelian genes have only been identified in a few families worldwide. Here we report the identification of an autosomal-dominant gene for hereditary spastic paraplegia (HSP) in 10 families that are of diverse geographic origin and whose affected members all carry unique truncating changes in a circumscript region of UBAP1 (ubiquitin-associated protein 1). HSP is a neurodegenerative disease characterized by progressive lower-limb spasticity and weakness, as well as frequent bladder dysfunction. At least 40% of affected persons are currently undiagnosed after exome sequencing. We identified pathological truncating variants in UBAP1 in affected persons from Iran, USA, Germany, Canada, Spain, and Bulgarian Roma. The genetic support ranges from linkage in the largest family (LOD = 8.3) to three confirmed de novo mutations. We show that mRNA in the fibroblasts of affected individuals escapes nonsense-mediated decay and thus leads to the expression of truncated proteins; in addition, concentrations of the full-length protein are reduced in comparison to those in controls. This suggests either a dominant-negative effect or haploinsufficiency. UBAP1 links endosomal trafficking to the ubiquitination machinery pathways that have been previously implicated in HSPs, and UBAP1 provides a bridge toward a more unified pathophysiology