Genetic and Structural Analysis of a SKIV2L Mutation Causing Tricho-hepato-enteric Syndrome.
Dig Dis Sci
; 63(5): 1192-1199, 2018 05.
Article
en En
| MEDLINE
| ID: mdl-29484573
ABSTRACT
BACKGROUND:
Advances in genomics have facilitated the discovery of monogenic disorders in patients with unique gastro-intestinal phenotypes. Syndromic diarrhea, also called tricho-hepato-enteric (THE) syndrome, results from deleterious mutations in SKIV2L or TTC37 genes. The main features of this disorder are intractable diarrhea, abnormal hair, facial dysmorphism, immunodeficiency and liver disease.AIM:
To report on a patient with THE syndrome and present the genetic analysis that facilitated diagnosis.METHODS:
Whole-exome sequencing (WES) was performed in a 4-month-old female with history of congenital diarrhea and severe failure to thrive but without hair anomalies or dysmorphism. Since the parents were first-degree cousins, the analysis focused on an autosomal recessive model. Sanger sequencing was used to validate suspected variants. Mutated protein structure was modeled to assess the effect of the mutation on protein function.RESULTS:
We identified an autosomal recessive C.1891G > A missense mutation (NM_006929) in SKIV2L gene that was previously described only in a compound heterozygous state as causing THE syndrome. The mutation was determined to be deleterious in multiple prediction models. Protein modeling suggested that the mutation has the potential to cause structural destabilization of SKIV2L, either through conformational changes, interference with the protein's packing, or changes at the protein's interface.CONCLUSIONS:
THE syndrome can present with a broad range of clinical features in the neonatal period. WES is an important diagnostic tool in patients with congenital diarrhea and can facilitate diagnosis of various diseases presenting with atypical features.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
ADN Helicasas
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Mutación Missense
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Diarrea Infantil
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Retardo del Crecimiento Fetal
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Enfermedades del Cabello
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
Idioma:
En
Revista:
Dig Dis Sci
Año:
2018
Tipo del documento:
Article