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Journal Articles Human Mutation Year : 2019

SLC35A2‐CDG: Functional characterization, expanded molecular, clinical, and biochemical phenotypes of 30 unreported Individuals

Lorenzo Botto
  • Function : Author
David Coman
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Abdallah Elias
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Trine Bjørg Hammer
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Jaclyn Haven
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Nicola Longo
Charles Marques Lourenço
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Ghayda Mirzaa
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Wendy Mitchell
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Hiltrud Muhle
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Stanley Nelson
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Mariusz Olczak
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Christina Palmer
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Arthur Partikian
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Marc Patterson
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Tyler Pierson
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Shane Quinonez
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Brigid Regan
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M Elizabeth Ross
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Maria Guillen Sacoto
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Fernando Scaglia
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Ingrid Scheffer
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Devorah Segal
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Nilika Shah Singhal
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Pasquale Striano
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Luisa Sturiale
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Joseph Symonds
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Sha Tang
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Eric Vilain
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Mary Willis
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Lynne Wolfe
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Hui Yang
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Shoji Yano
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Zöe Powis
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Sharon Suchy
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Jill Rosenfeld
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Andrew Edmondson
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Stephanie Grunewald
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Hudson Freeze
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Abstract

Pathogenic de novo variants in the X-linked gene SLC35A2 encoding the major Golgi-localized UDP-galactose transporter required for proper protein and lipid glycosylation cause a rare type of congenital disorder of glycosylation known as SLC35A2-congenital disorders of glycosylation (CDG; formerly CDG-IIm). To date, 29 unique de novo variants from 32 unrelated individuals have been described in the literature. The majority of affected individuals are primarily characterized by varying degrees of neurological impairments with or without skeletal abnormalities. Surprisingly, most affected individuals do not show abnormalities in serum transferrin N-glycosylation, a common biomarker for most types of CDG. Here we present data characterizing 30 individuals and add 26 new variants, the single largest study involving SLC35A2-CDG. The great majority of these individuals had normal transferrin glycosylation. In addition, expanding the molecular and clinical spectrum of this rare disorder, we developed a robust and reliable biochemical assay to assess SLC35A2-dependent UDP-galactose transport activity in primary fibroblasts. Finally, we show that transport activity is directly correlated to the ratio of wild-type to mutant alleles in fibroblasts from affected individuals.

Dates and versions

hal-04566306 , version 1 (02-05-2024)

Identifiers

Cite

Bobby Ng, Paulina Sosicka, Satish Agadi, Mohammed Almannai, Carlos Bacino, et al.. SLC35A2‐CDG: Functional characterization, expanded molecular, clinical, and biochemical phenotypes of 30 unreported Individuals. Human Mutation, 2019, 40 (7), pp.humu.23731. ⟨10.1002/humu.23731⟩. ⟨hal-04566306⟩
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