Genotypes and estimated prevalence of phosphomannomutase 2 deficiency in Turkey differ significantly from those in Europe.
Am J Med Genet A
; 182(4): 705-712, 2020 04.
Article
em En
| MEDLINE
| ID: mdl-31981409
ABSTRACT
Phosphomannomutase 2 deficiency (PMM2-CDG) is an autosomal recessive congenital disorder of glycosylation, characterized by multisystem phenotypes, mostly including neurological involvement. In Turkey, due to high rates of consanguinity, many patients with autosomal recessive disorders have homozygous variants and these diseases are more common, compared to Europe. However, published reports of PMM2-CDG from Turkey are scarce. Here, we describe clinical and molecular characteristics of PMM2-CDG patients diagnosed in three centers in Turkey, using data obtained retrospectively from hospital records. We also analyzed an in-house exome database of 1,313 individuals for PMM2 variants and estimated allele, carrier and disease frequencies, using the Hardy-Weinberg law. Eleven patients were identified from 10 families, displaying similar characteristics to previous publications, with the exception of the first report of epilepsia partialis continua and increased prevalence of sensorineural hearing loss. p.Val231Met was the most common variant, and was homozygous in four patients. This novel genotype results in a neurological phenotype with subclinical visceral involvement. Exome database analysis showed an estimated prevalence of 1286,726 for PMM2-CDG, which is much lower than expected (120,000 in Europe) because of the lack of predominance of the common European p.Asp141His allele, associated with a severe phenotype (allele frequency of 12,622 compared to 1252 in gnomAD). These data suggest that prevalence, phenotypes and genotypes of PMM2-CDG in Turkey differ significantly from those in Europe Milder phenotypes may be more common, but the disease itself rarer, requiring a higher clinical suspicion for diagnosis. The association of sensorineural hearing loss with PMM2-CDG warrants further study.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfotransferases (Fosfomutases)
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Defeitos Congênitos da Glicosilação
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Mutação
Tipo de estudo:
Observational_studies
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Prevalence_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Child
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Child, preschool
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Female
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Humans
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Infant
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Male
País/Região como assunto:
Asia
Idioma:
En
Revista:
Am J Med Genet A
Ano de publicação:
2020
Tipo de documento:
Article