Genotypes and estimated prevalence of phosphomannomutase 2 deficiency in Turkey differ significantly from those in Europe |
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Authors: | Y?lmaz Y?ld?z Mutluay Arslan Gökalp Çelik Çi?dem Seher Kasapkara Serdar Ceylaner Ali Dursun Hatice Serap Sivri Turgay Co?kun Ay?egül Tokatl? |
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Institution: | 1. https://orcid.org/0000-0001-9076-1388;2. Faculty of Medicine, Department of Pediatrics, Division of Pediatric Metabolism, Hacettepe University, Ankara, Turkey;3. Dr. Sami Ulus Teaching and Research Hospital for Maternal and Child Health, Pediatric Metabolic Diseases Unit, Ankara, Turkey;4. Gülhane Teaching and Research Hospital, Pediatric Metabolism Unit, University of Health Sciences, Ankara, Turkey;5. Y?lmaz Y?ld?z, Dr. Sami Ulus Kad?n Do?um, ?ocuk Sa?l??? ve Hastal?klar? E?itim ve Ara?t?rma Hastanesi, Merkez Bina, Babür Caddesi, No: 44, 06080, Alt?nda?, Ankara, Turkey.;6. Gülhane Teaching and Research Hospital, Department of Pediatrics, Division of Pediatric Neurology, University of Health Sciences, Ankara, Turkey;7. ?ntergen Genetic Diagnosis Center, Ankara, Turkey;8. Faculty of Medicine, Department of Pediatrics, Y?ld?r?m Beyaz?t University, Ankara, Turkey |
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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 1:286,726 for PMM2‐CDG, which is much lower than expected (1:20,000 in Europe) because of the lack of predominance of the common European p.Asp141His allele, associated with a severe phenotype (allele frequency of 1:2,622 compared to 1:252 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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Keywords: | congenital disorder(s) of glycosylation phosphomannomutase 2 deficiency PMM2‐CDG population genetics sensorineural hearing loss |
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