Abstract

Rafiq syndrome is a congenital disorder of glycosylation type II that develops due to mutations in the Mannosidase Alpha Class 1B Member 1 (MAN1B1) gene encoding α 1,2-mannosidase. In the literature, 45 patients have been reported to date. This study presents a patient with some phenotypic traits that differ from previously reported patients with Rafiq syndrome.Since the patient was not diagnosed despite detailed examinations, whole exome sequencing was performed. The patientss’ homozygous c.1000 C>T (p.Arg334Cys) pathogenic variant was detected in the MAN1B1 gene (NM_016219.5), which was consistent with Rafiq syndrome. Our patient’s clinical findings were mainly similar to those of previously reported patients. However, our patient had feeding difficulty that started to improve after the fifth month and persistent hyperekplexia .
Feeding difficulty and hyperekplexia concomitant to MAN1B1 gene mutation are reported for the first time. More extensive case series are needed to understand whether these findings are part of the syndrome or incidental comorbid conditions

Keywords: Congenital Disorder of Glycosylation, Rafiq syndrome, MAN1B1 Gene Mutation, Hyperekplexia How to Cite

Özgün, N., & Merve Saka Güvenç, M. (2025). Rafiq Syndrome: Old Variant in MAN1B1 Gene and Some New Phenotypic Features. Iranian Journal of Child Neurology, 19(1), 121–126. https://doi.org/10.22037/ijcn.v19i1.42376

References

References
1. Sosicka P, Ng BG, Freeze HH. Chemical Therapies for Congenital Disorders of Glycosylation. ACS Chem Biol. 2022;17(11):2962–71.
2. Rafiq MA, Kuss AW, Puettmann L, Noor A, Ramiah A, Ali G, et al. Mutations in the alpha 1,2-mannosidase gene, MAN1B1, cause autosomal-recessive intellectual disability. Am J Hum Genet [Internet]. 2011;89(1):176–82. Available from: http://dx.doi.org/10.1016/j.ajhg.2011.06.006
3. Sosicka P, Ng BG, Freeze HH. Congenital Disorders of Glycosylation. Compr Glycosci Second Ed. 2021;6(24):294–334.
4. Kasapkara CS, Olgac A, Kilic M, Keldermans L, Matthijs G, Jaeken J. MAN1B1-CDG: Novel patients and novel variant. J Pediatr Endocrinol Metab. 2021;34(9):1207–9.
5. Entrez Gene NCBI. MAN1A1 mannosidase alpha class 1A member 1 [Homo sapiens (human)] [Internet]. 2021 [cited 2023 Mar 29]. Available from: https://www.ncbi.nlm.nih.gov/gene/4121
6. National Library of Medicine. Rafiq Syndrome [Internet]. 2023. Available from: https://www.ncbi.nlm.nih.gov/medgen/481757#:~:text=A delay in the achievement,and social and emotional skills.
7. Greczan M, Rokicki D, Wesół-Kucharska D, Kaczor M, Rawiak A, Jezela-Stanek A. Perinatal manifestations of congenital disorders of glycosylation—A clue to early diagnosis. Front Genet. 2022;13(December):1–8.
8. Gonzalez DS, Karaveg K, Vandersall-Nairn AS, Lal A, Moremen KW. Identification, expression, and characterization of a cDNA encoding human endoplasmic reticulum mannosidase I, the enzyme that catalyzes the first mannose trimming step in mammalian Asn-linked oligosaccharide biosynthesis. J Biol Chem [Internet]. 1999;274(30):21375–86. Available from: http://dx.doi.org/10.1074/jbc.274.30.21375
9. Zhan F xia, Wang SG, Cao L. Advances in hyperekplexia and other startle syndromes. Neurol Sci [Internet]. 2021;42(10):4095–107. Available from: https://doi.org/10.1007/s10072-021-05493-8
10. Saini AG, Pandey S. Hyperekplexia and other startle syndromes. J Neurol Sci [Internet]. 2020;416(July):117051. Available from: https://doi.org/10.1016/j.jns.2020.117051

Abstract Viewed: 61 times