PRPS1 loss-of-function variants, from isolated hearing loss to severe congenital encephalopathy: New cases and literature review

We describe two sporadic and two familial cases with loss-of-function variants in PRPS1, which is located on the X chromosome and encodes phosphoribosyl pyrophosphate synthetase 1 (PRS-1). We illustrate the clinical variability associated with decreased PRS-1 activity, ranging from mild isolated hea...

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Bibliographic Details
Published in:European journal of medical genetics 2020-11, Vol.63 (11), p.104033-104033, Article 104033
Main Authors: Mercati, Oriane, Abi Warde, Marie-Thérèse, Lina-Granade, Geneviève, Rio, Marlène, Heide, Solveig, de Lonlay, Pascale, Ceballos-Picot, Irène, Robert, Matthieu P., Couloigner, Vincent, Beltrand, Jacques, Boddaert, Nathalie, Rodriguez, Diana, Rubinato, Elisa, Lapierre, Jean-Michel, Merlette, Christophe, Sanquer, Sylvia, Rötig, Agnès, Prokisch, Holger, Lyonnet, Stanislas, Loundon, Natalie, Kaplan, Josseline, Bonnefont, Jean-Paul, Munnich, Arnold, Besmond, Claude, Jonard, Laurence, Marlin, Sandrine
Format: Article
Language:English
Subjects:
Arts syndrome
Ataxia - genetics
Ataxia - pathology
Child
Deaf-Blind Disorders - genetics
Deaf-Blind Disorders - pathology
Deafness
Female
Genetic Diseases, X-Linked - genetics
Genetic Diseases, X-Linked - pathology
Hearing loss
Humans
Infant
Intellectual deficiency
Intellectual Disability - genetics
Intellectual Disability - pathology
Life Sciences
Loss of Function Mutation
Male
Pedigree
Phenotype
PRPS1
Ribose-Phosphate Pyrophosphokinase - genetics
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Summary:We describe two sporadic and two familial cases with loss-of-function variants in PRPS1, which is located on the X chromosome and encodes phosphoribosyl pyrophosphate synthetase 1 (PRS-1). We illustrate the clinical variability associated with decreased PRS-1 activity, ranging from mild isolated hearing loss to severe encephalopathy. One of the variants we identified has already been reported with a phenotype similar to our patient's, whereas the other three were unknown. The clinical and biochemical information we provide will hopefully contribute to gain insight into the correlation between genotype and phenotype of this rare condition, both in females and in males. Moreover, our observation of a new family in which hemizygous males display hearing loss without any neurological or ophthalmological symptoms prompts us to suggest analysing PRPS1 in cases of isolated hearing loss. Eventually, PRPS1 variants should be considered as a differential diagnosis of mitochondrial disorders.
ISSN:1769-7212
1878-0849
DOI:10.1016/j.ejmg.2020.104033