B3galnt2 Mutations Associated With Non-Syndromic Autosomal Recessive Intellectual Disability Reveal a Lack of Genotype-Phenotype Associations in the Muscular Dystrophy-Dystroglycanopathies

B3galnt2 Mutations Associated With Non-Syndromic Autosomal Recessive Intellectual Disability Reveal a Lack of Genotype-Phenotype Associations in the Muscular Dystrophy-Dystroglycanopathies Publisher Pubmed

Maroofian R¹ ; Riemersma M^{2, 3, 4} ; Jae LT⁵ ; Zhianabed N⁶ ; Willemsen MH⁴ ; Wissinklindhout WM⁴ ; Willemsen MA² ; De Brouwer APM⁴ ; Mehrjardi MYV⁷ ; Ashrafi MR⁸ ; Kusters B^{9, 10} ; Kleefstra T⁴ ; Jamshidi Y¹ ; Nasseri M^{6, 11} Show All Authors

Maroofian R¹
Riemersma M^{2, 3, 4}
Jae LT⁵
Zhianabed N⁶
Willemsen MH⁴
Wissinklindhout WM⁴
Willemsen MA²
De Brouwer APM⁴
Mehrjardi MYV⁷
Ashrafi MR⁸
Kusters B^{9, 10}
Kleefstra T⁴
Jamshidi Y¹
Nasseri M^{6, 11}
Pfundt R⁴
Brummelkamp TR⁵
Abbaszadegan MR^{6, 12}
Lefeber DJ^{2, 3}
Van Bokhoven H⁴

Show Affiliations

1. St George's University of London, Cranmer Terrace, Genetics and Molecular Cell Sciences Research Centre, London, SW17 0RE, United Kingdom
2. Radboud university medical center, Department of Neurology, Geert Grooteplein 10, Nijmegen, 6525 GA, Netherlands
3. Radboud university medical center, Department of Laboratory Medicine, Geert Grooteplein 10, Nijmegen, 6525 GA, Netherlands
4. Radboud university medical center, Department of Human Genetics 855, Donders Institute for Brain, Cognition and Behaviour, Geert Grooteplein 10, Nijmegen, 6525 GA, Netherlands
5. Ludwig-Maximilians-Universitat Munchen, Gene Center and Department of Biochemistry, Feodor-Lynen-StraÃŸe 25, Munich, 81377, Germany
6. Pardis Clinical and Genetics Laboratory, Mashhad, Iran
7. Shahid Sadoughi University of Medical Sciences, Medical Genetics Research Center, Yazd, Iran
8. Tehran University of Medical Sciences, Department of Child Neurology, Children's Medical Center, Tehran, Iran
9. Radboud university medical center, Department of Pathology, Geert Grooteplein 10, Nijmegen, 6525 GA, Netherlands
10. Maastricht University Medical Centre, Department of Pathology, Maastricht, 6229 HX, Netherlands
11. Mashhad University of Medical Sciences, Medical Genetics Research Center, Mashhad, Iran
12. Mashhad University of Medical Sciences, Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad, Iran

Source: Genome Medicine Published:2017

Abstract

Background: The phenotypic severity of congenital muscular dystrophy-dystroglycanopathy (MDDG) syndromes associated with aberrant glycosylation of α-dystroglycan ranges from the severe Walker-Warburg syndrome or muscle-eye-brain disease to mild, late-onset, isolated limb-girdle muscular dystrophy without neural involvement. However, muscular dystrophy is invariably found across the spectrum of MDDG patients. Methods: Using linkage mapping and whole-exome sequencing in two families with an unexplained neurodevelopmental disorder, we have identified homozygous and compound heterozygous mutations in B3GALNT2. Results: The first family comprises two brothers of Dutch non-consanguineous parents presenting with mild ID and behavioral problems. Immunohistochemical analysis of muscle biopsy revealed no significant aberrations, in line with the absence of a muscular phenotype in the affected siblings. The second family includes five affected individuals from an Iranian consanguineous kindred with mild-to-moderate intellectual disability (ID) and epilepsy without any notable neuroimaging, muscle, or eye abnormalities. Complementation assays of the compound heterozygous mutations identified in the two brothers had a comparable effect on the O-glycosylation of α-dystroglycan as previously reported mutations that are associated with severe muscular phenotypes. Conclusions: In conclusion, we show that mutations in B3GALNT2 can give rise to a novel MDDG syndrome presentation, characterized by ID associated variably with seizure, but without any apparent muscular involvement. Importantly, B3GALNT2 activity does not fully correlate with the severity of the phenotype as assessed by the complementation assay. © 2017 The Author(s).

2. A Two-Color Haploid Genetic Screen Identifies Novel Host Factors Involved in Hiv-1 Latency, mBio (2021)

3. Poglut1 Biallelic Mutations Cause Myopathy With Reduced Satellite Cells, Α-Dystroglycan Hypoglycosylation and a Distinctive Radiological Pattern, Acta Neuropathologica (2020)

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Shahriar Nafissi (2)

Style	Citing Format
MLA	Maroofian R, et al.. "B3galnt2 Mutations Associated With Non-Syndromic Autosomal Recessive Intellectual Disability Reveal a Lack of Genotype-Phenotype Associations in the Muscular Dystrophy-Dystroglycanopathies." Genome Medicine, vol. 9, no. 1, 2017, pp. -.
APA	Maroofian R, Riemersma M, Jae LT, Zhianabed N, Willemsen MH, Wissinklindhout WM, Willemsen MA, De Brouwer APM, Mehrjardi MYV, Ashrafi MR, Kusters B, Kleefstra T, Jamshidi Y, Nasseri M, Pfundt R, Brummelkamp TR, Abbaszadegan MR, Lefeber DJ, Van Bokhoven H (2017). B3galnt2 Mutations Associated With Non-Syndromic Autosomal Recessive Intellectual Disability Reveal a Lack of Genotype-Phenotype Associations in the Muscular Dystrophy-Dystroglycanopathies. Genome Medicine, 9(1), -.
Chicago	Maroofian R, Riemersma M, Jae LT, Zhianabed N, Willemsen MH, Wissinklindhout WM, Willemsen MA, et al.. "B3galnt2 Mutations Associated With Non-Syndromic Autosomal Recessive Intellectual Disability Reveal a Lack of Genotype-Phenotype Associations in the Muscular Dystrophy-Dystroglycanopathies." Genome Medicine 9, no. 1 (2017): -.
Harvard	Maroofian R et al. (2017) 'B3galnt2 Mutations Associated With Non-Syndromic Autosomal Recessive Intellectual Disability Reveal a Lack of Genotype-Phenotype Associations in the Muscular Dystrophy-Dystroglycanopathies', Genome Medicine, 9(1), pp. -.
Vancouver	Maroofian R, Riemersma M, Jae LT, Zhianabed N, Willemsen MH, Wissinklindhout WM, et al.. B3galnt2 Mutations Associated With Non-Syndromic Autosomal Recessive Intellectual Disability Reveal a Lack of Genotype-Phenotype Associations in the Muscular Dystrophy-Dystroglycanopathies. Genome Medicine. 2017;9(1):-.
BibTex	@article{ author = {Maroofian R and Riemersma M and Jae LT and Zhianabed N and Willemsen MH and Wissinklindhout WM and Willemsen MA and De Brouwer APM and Mehrjardi MYV and Ashrafi MR and Kusters B and Kleefstra T and Jamshidi Y and Nasseri M and Pfundt R and Brummelkamp TR and Abbaszadegan MR and Lefeber DJ and Van Bokhoven H}, title = {B3galnt2 Mutations Associated With Non-Syndromic Autosomal Recessive Intellectual Disability Reveal a Lack of Genotype-Phenotype Associations in the Muscular Dystrophy-Dystroglycanopathies}, journal = {Genome Medicine}, volume = {9}, number = {1}, pages = {-}, year = {2017} }
RIS	TY - JOUR AU - Maroofian R AU - Riemersma M AU - Jae LT AU - Zhianabed N AU - Willemsen MH AU - Wissinklindhout WM AU - Willemsen MA AU - De Brouwer APM AU - Mehrjardi MYV AU - Ashrafi MR AU - Kusters B AU - Kleefstra T AU - Jamshidi Y AU - Nasseri M AU - Pfundt R AU - Brummelkamp TR AU - Abbaszadegan MR AU - Lefeber DJ AU - Van Bokhoven H TI - B3galnt2 Mutations Associated With Non-Syndromic Autosomal Recessive Intellectual Disability Reveal a Lack of Genotype-Phenotype Associations in the Muscular Dystrophy-Dystroglycanopathies JO - Genome Medicine VL - 9 IS - 1 SP - EP - PY - 2017 ER -

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