Congenital sodium diarrhea and chorioretinal coloboma with optic disc coloboma in a patient with biallelic SPINT2 mutations, including p.(Tyr163Cys)

Autor: Bryce A. Mendelsohn, Anthony T. Moore, Aditi Chawla, Ryan J. Taft, Anne Slavotinek, Denise L. Perry, Duncan Henry, Kristin E. Hirabayashi
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
DNA Mutational Analysis
Choanal atresia
Eye
Gastroenterology
Congenital
2.1 Biological and endogenous factors
Aetiology
Genetics (clinical)
Pediatric
Coloboma
Membrane Glycoproteins
Ophthalmoscopes
Diarrhea
Phenotype
keratitis
Optic nerve
medicine.symptom
Hyponatremia
congenital sodium diarrhea
Optic nerve coloboma
medicine.medical_specialty
Clinical Sciences
ocular findings with SPINT2
Article
03 medical and health sciences
congenital tufting enteropathy
Clinical Research
Internal medicine
medicine
Genetics
Humans
Eye Disease and Disorders of Vision
Alleles
Genetic Association Studies
eye findings with SPINT2
Whole Genome Sequencing
business.industry
Facies
Infant
Optic Nerve
SPINT2
medicine.disease
Congenital tufting enteropathy
eye diseases
030104 developmental biology
Amino Acid Substitution
Mutation
sense organs
corneal erosions
business
Imperforate anus
Zdroj: American journal of medical genetics. Part A, vol 176, iss 4
Popis: Congenital sodium diarrhea is a rare and life-threatening disorder characterized by a severe, secretory diarrhea containing high concentrations of sodium, leading to hyponatremia and metabolic acidosis. It may occur in isolation or in association with systemic features such as facial dysmorphism, choanal atresia, imperforate anus, and corneal erosions. Mutations in the serine protease inhibitor, Kunitz-Type 2 (SPINT2) gene have been associated with congenital sodium diarrhea and additional syndromic features. We present a child with congenital sodium diarrhea, cleft lip and palate, corneal erosions, optic nerve coloboma, and intermittent exotropia who was found to have biallelic mutations in SPINT2. One mutation, c.488A > G, predicting p.(Tyr163Cys), has been previously associated with a syndromic form of congenital sodium diarrhea. The other mutation, c.166_167dupTA, predicting p.(Asn57Thrfs*24) has not previously been reported and is likely a novel pathogenic variant for this disorder. We found only one other report of an optic nerve coloboma associated with SPINT2 mutations and this occurred in a patient with congenital tufting enteropathy. Our patient confirms an association of ocular coloboma with presumed loss of SPINT2 function.
Databáze: OpenAIRE