Case Report: A Novel Homozygous Frameshift Mutation of the SKIV2L Gene in a Trichohepatoenteric Syndrome Patient Presenting With Short Stature, Premature Ovarian Failure, and Osteoporosis

Abstract

Background: Trichohepatoenteric syndrome (THES) is a rare Mendelian autosomal recessive genetic disease characterized by intractable diarrhea, woolly hair, facial abnormality, immune dysfunction, and intrauterine growth restriction. THES mutations are found in the TTC37 and SKIV2L genes, which encode two components of the human superkiller (SKI) complex.Methods and results: We report one case of a 32-year-old woman of Chinese descent with THES, who was born with a low weight (2000 g). She had intractable diarrhea during the neonatal period and was allergic to cow’s milk and condensed milk, but did not require total parenteral nutrition. She experienced menarche at age 12 and amenorrhea at age 28. In May 2019, the patient presented with a left fibular head fracture and was diagnosed with osteoporosis. Genetic testing showed a novel mutation in exon1 [p.E5Afs∗37 (c.12_13del)] of SKIV2L, which is composed of 28 exons. After the diagnosis, hormone replacement therapy was prescribed, in addition to the routine calcium and vitamin D supplements.Conclusion: This case expands the clinical characteristic and phenotype spectrum of THES, providing further understanding of SKIV2L and its autoimmune influence.

The Role of Thickened Nuchal Translucency on Copy Number Variations and Pregnancy Outcomes in Northeast Coast of Fujian Province, China: A Comparison Between Traditional Karyotyping and Single Nucleotide Polymorphism Array Analysis

“…Moreover, SNP array analysis revealed an 11.7Mb LOH on 6p22.3p21.31 in foetus 6. 6p22.3p21.31 contains VARS2, SKIV2L, and 39 other genes related to autosomal recessive diseases [39,40]. Studies have reported clinical phenotypes including foetal developmental delays, hyperglycaemia, and dehydration [41].…”

SKI complex: A multifaceted cytoplasmic RNA exosome cofactor in mRNA metabolism with links to disease, developmental processes, and antiviral responses

“…Some authors expand this spectrum of clinical signs by two less frequent symptoms, that is, (8) congenital cardiac defects (particularly in the Asian population; Fabre et al, 2012, 2013, 2014, 2017; W. I. Lee et al, 2016); and (9) platelet abnormalities (Fabre et al, 2012, 2013, 2014, 2017; Hartley et al, 2010). Other anomalies detected in THES patients include: enteric symptoms (colitis, intestinal villous atrophy; abnormal sorting and/or decreased expression of several brush‐border transport proteins, such as: Na + /H + exchangers, aquaporin 7, Na + /I − symporter and the H + /K + ATPase, on the apical surface of jejunal enterocytes, was demonstrated by immunohistochemistry; Hartley et al, 2010), hypoglycemia (Gao et al, 2022; Xinias et al, 2018), dental abnormalities (Karaca Edeer et al, 2019), premature birth with low birth weight (Fabre et al, 2012; Fabre et al, 2013), short stature (below third percentile in 50% of individuals; Fabre et al, 2014; M. Yang, Jiang, et al, 2022), and mild mental retardation (Fabre et al, 2014). Due to such a wide spectrum of symptoms, the prognosis is poor and one of THES characteristics is high mortality rate (up to 50%)—many patients die before the age of 5–10 and just a few affected individuals survived up to the third decade (Fabre et al, 2014).…”

“…Curiously though, theoretically less harmful mut 7 in the homozygous state was associated with later onset diarrhea and severe combined immunodeficiency in a patient, who additionally presented with Pneumocystis jirovicii pneumonia (PJP) and postnatally acquired CMV infection (Hosking et al, 2018). On the other hand, the female patient with homozygous mutation leading to production of the most severely truncated SKI2W among all cases studied (c.12_13 delAG, p.Glu5Ala fs*37; mut 1 ; Table 3 and Figure 11b), who suffered from mild diarrhea in the neonatal period, was able to survive until the age of >30 years, which allowed to observe novel symptoms, that is, premature menopause and osteoporosis (M. Yang, Jiang, et al, 2022). All these examples show that it is virtually impossible to capture any logical correlation between specific genotypes and phenotypes of THES patients.…”