Clinical Spectrum Associated with Wolfram Syndrome Type 1 and Type 2: A Review on Genotype–Phenotype Correlations

Maurizio Delvecchio, Matteo Iacoviello, Antonino Pantaleo and Nicoletta Resta
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Maurizio Delvecchio: Metabolic Diseases, Clinical Genetics and Diabetology Unit, Giovanni XXIII Children’s Hospital, 70126 Bari, Italy
Matteo Iacoviello: Department of Biomedical Sciences and Human Oncology (DIMO), Division of Medical Genetics, University of Bari “Aldo Moro”, 70124 Bari, Italy
Antonino Pantaleo: Department of Biomedical Sciences and Human Oncology (DIMO), Division of Medical Genetics, University of Bari “Aldo Moro”, 70124 Bari, Italy
Nicoletta Resta: Department of Biomedical Sciences and Human Oncology (DIMO), Division of Medical Genetics, University of Bari “Aldo Moro”, 70124 Bari, Italy

IJERPH, 2021, vol. 18, issue 9, 1-12

Abstract: Wolfram syndrome is a rare neurodegenerative disorder that is typically characterized by diabetes mellitus and optic atrophy. Other common features are diabetes insipidus and hearing loss, but additional less-frequent findings may also be present. The phenotype spectrum is quite wide, and penetrance may be incomplete. The syndrome is progressive, and thus, the clinical picture may change during follow-up. Currently, two different subtypes of this syndrome have been described, and they are associated with two different disease-genes, wolframin ( WFS1 ) and CISD2 . These genes encode a transmembrane protein and an endoplasmic reticulum intermembrane protein, respectively. These genes are detected in different organs and account for the pleiotropic features of this syndrome. In this review, we describe the phenotypes of both syndromes and discuss the most pertinent literature about the genotype–phenotype correlation. The clinical presentation of Wolfram syndrome type 1 suggests that the pathogenic variant does not predict the phenotype. There are few papers on Wolfram syndrome type 2 and, thus, predicting the phenotype on the basis of genotype is not yet supported. We also discuss the most pertinent approach to gene analysis.

Keywords: Wolfram syndrome; wolframin; ERIS; CISD2; molecular genetics; genotype-phenotype correlation; diabetes mellitus; optic atrophy; sensorineural hearing loss; diabetes insipidus (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2021
References: View complete reference list from CitEc
Citations: View citations in EconPapers (4)

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