Send to

Choose Destination
J Hum Genet. 2016 Jul;61(7):577-83. doi: 10.1038/jhg.2016.30. Epub 2016 Mar 31.

Exome sequencing reveals two novel compound heterozygous XYLT1 mutations in a Polish patient with Desbuquois dysplasia type 2 and growth hormone deficiency.

Author information

Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland.
NZOZ Center for Medical Genetics GENESIS, Poznan, Poland.
Department of Medical Imaging, The Children's Hospital at Westmead, Sydney, NSW, Australia.
Department of Pediatric Endocrinology and Rheumatology, Poznan University of Medical Sciences, Poznan, Poland.
Karol Jonscher's Clinical Hospital, Poznan University of Medical Sciences, Poznan, Poland.
Department of Transplantology, General, Vascular and Plastic Surgery Clinical Hospital of Poznan University of Medical Sciences, Poznan, Poland.
Institute for Medical Genetics and Human Genetics, Charité Universitätsmedizin Berlin, Berlin, Germany.
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.
Labor Berlin-Charité Vivantes GmbH, Humangenetik, Berlin, Germany.


Desbuquois dysplasia type 2 (DBQD2) is a rare recessively inherited skeletal genetic disorder characterized by severe prenatal and postnatal growth retardation, generalized joint laxity with dislocation of large joints and facial dysmorphism. The condition was recently described to result from autosomal recessive mutations in XYLT1, encoding the enzyme xylosyltransferase-1. In this paper, we report on a Polish patient with DBQD2 who presented with severe short stature of prenatal onset, joint laxity, psychomotor retardation and multiple radiological abnormalities including short metacarpals, advanced bone age and exaggerated trochanters. Endocrinological examinations revealed that sleep-induced growth hormone (GH) release and GH peak in clonidine- and glucagon-induced provocative tests as well as insulin-like growth factor 1 (IGF-1) and IGF-binding protein-3 levels were all markedly decreased, confirming deficiency of GH secretion. Bone age, unlikely to GH deficiency, was significantly advanced. To establish the diagnosis at a molecular level, we performed whole-exome sequencing and bioinformatic analysis in the index patient, which revealed compound heterozygous XYLT1 mutations: c.595C>T(p.Gln199*) and c.1651C>T(p.Arg551Cys), both of which are novel. Sanger sequencing showed that the former mutation was inherited from the healthy mother, whereas the latter one most probably occurred de novo. Our study describes the first case of DBQD2 resulting from compound heterozygous XYLT1 mutation, expands the mutational spectrum of the disease and provides evidence that the severe growth retardation and microsomia observed in DBQD2 patients may result not only from the skeletal dysplasia itself but also from GH and IGF-1 deficiency.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center