TY - JOUR
T1 - Broadening the phenotypic spectrum of Beta3GalT6-associated phenotypes
AU - Leoni, Chiara
AU - Tedesco, Marta
AU - Radio, Francesca Clementina
AU - Chillemi, Giovanni
AU - Leone, Antonio
AU - Bruselles, Alessandro
AU - Ciolfi, Andrea
AU - Stellacci, Emilia
AU - Pantaleoni, Francesca
AU - Butera, Gianfranco
AU - Rigante, Donato
AU - Onesimo, Roberta
AU - Tartaglia, Marco
AU - Zampino, Giuseppe
N1 - Funding Information:
The authors thank the participating family and Serenella Venanzi (Istituto Superiore di Sanit?, Rome) for technical assistance. This work was supported, in part, by funding from Fondazione Bambino Ges? (Vite Coraggiose to Marco Tartaglia), and Italian Ministry of Health (CCR-2017-23669081 to Marco Tartaglia; RCR-2020-23670068_001 to Marco Tartaglia and Giuseppe Zampino; RF-2018-12366931 to Francesca Clementina Radio and Giovanni Chillemi).
Funding Information:
The authors thank the participating family and Serenella Venanzi (Istituto Superiore di Sanità, Rome) for technical assistance. This work was supported, in part, by funding from Fondazione Bambino Gesù (Vite Coraggiose to Marco Tartaglia), and Italian Ministry of Health (CCR‐2017‐23669081 to Marco Tartaglia; RCR‐2020‐23670068_001 to Marco Tartaglia and Giuseppe Zampino; RF‐2018‐12366931 to Francesca Clementina Radio and Giovanni Chillemi).
Publisher Copyright:
© 2021 Wiley Periodicals LLC.
PY - 2021/10
Y1 - 2021/10
N2 - Biallelic mutations in B3GALT6, coding for a galactosyltransferase involved in the synthesis of glycosaminoglycans (GAGs), have been associated with various clinical conditions, causing spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMDJL1 or SEMDJL Beighton type), Al-Gazali syndrome (ALGAZ), and a severe progeroid form of Ehlers-Danlos syndrome (EDSSPD2). In the 2017 Ehlers-Danlos syndrome (EDS) classification, Beta3GalT6-related disorders were grouped in the spondylodysplastic EDSs together with spondylodysplastic EDSs due to B4GALT7 and SLC39A13 mutations. Herein, we describe a patient with a previously unreported homozygous pathogenic B3GALT6 variant resulting in a complex phenotype more severe than spondyloepimetaphyseal dysplasia with joint laxity type 1, and having dural ectasia and aortic dilation as additionally associated features, further broadening the phenotypic spectrum of the Beta3GalT6-related syndromes. We also document the utility of repeating sequencing in patients with uninformative exomes, particularly when performed by using “first generations” enrichment capture methods.
AB - Biallelic mutations in B3GALT6, coding for a galactosyltransferase involved in the synthesis of glycosaminoglycans (GAGs), have been associated with various clinical conditions, causing spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMDJL1 or SEMDJL Beighton type), Al-Gazali syndrome (ALGAZ), and a severe progeroid form of Ehlers-Danlos syndrome (EDSSPD2). In the 2017 Ehlers-Danlos syndrome (EDS) classification, Beta3GalT6-related disorders were grouped in the spondylodysplastic EDSs together with spondylodysplastic EDSs due to B4GALT7 and SLC39A13 mutations. Herein, we describe a patient with a previously unreported homozygous pathogenic B3GALT6 variant resulting in a complex phenotype more severe than spondyloepimetaphyseal dysplasia with joint laxity type 1, and having dural ectasia and aortic dilation as additionally associated features, further broadening the phenotypic spectrum of the Beta3GalT6-related syndromes. We also document the utility of repeating sequencing in patients with uninformative exomes, particularly when performed by using “first generations” enrichment capture methods.
KW - Al-Gazali syndrome
KW - B3GALT6
KW - Beta3GalT6
KW - dural ectasia
KW - spondylodysplastic Ehlers-Danlos syndrome
KW - spondyloepimetaphyseal dysplasia with joint laxity type 1
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UR - http://www.scopus.com/inward/citedby.url?scp=85108317178&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.62399
DO - 10.1002/ajmg.a.62399
M3 - Article
C2 - 34159694
AN - SCOPUS:85108317178
VL - 185
SP - 3153
EP - 3160
JO - Am. J. Med. Genet. Part A
JF - Am. J. Med. Genet. Part A
SN - 1552-4825
IS - 10
ER -