Novel Splicing Mutation in B3GAT3 Associated with Short Stature, GH Deficiency, Hypoglycaemia, Developmental Delay, and Multiple Congenital Anomalies
B3GAT3, encoding β-1,3-glucuronyltransferase 3, has an important role in proteoglycan biosynthesis. Homozygous B3GAT3 mutations have been associated with short stature, skeletal deformities, and congenital heart defects. We describe for the first time a novel heterozygous splice site mutation in B3G...
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Wiley
2017-01-01
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| Series: | Case Reports in Genetics |
| Online Access: | http://dx.doi.org/10.1155/2017/3941483 |
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| author | Samuel Bloor Dinesh Giri Mohammed Didi Senthil Senniappan |
| author_facet | Samuel Bloor Dinesh Giri Mohammed Didi Senthil Senniappan |
| author_sort | Samuel Bloor |
| collection | DOAJ |
| description | B3GAT3, encoding β-1,3-glucuronyltransferase 3, has an important role in proteoglycan biosynthesis. Homozygous B3GAT3 mutations have been associated with short stature, skeletal deformities, and congenital heart defects. We describe for the first time a novel heterozygous splice site mutation in B3GAT3 contributing to severe short stature, growth hormone (GH) deficiency, recurrent ketotic hypoglycaemia, facial dysmorphism, and congenital heart defects. A female infant, born at 34 weeks’ gestation to nonconsanguineous Caucasian parents with a birth weight of 1.9 kg, was noted to have cloacal abnormality, ventricular septal defect, pulmonary stenosis, and congenital sensorineural deafness. At 4 years of age, she was diagnosed with GH deficiency due to her short stature (height < 2.5 SD). MRI of the pituitary gland revealed a small anterior pituitary. She has multiple dysmorphic features: anteverted nares, small upturned nose, hypertelorism, slight frontal bossing, short proximal bones, hypermobile joints, and downslanting palpebral fissures. Whole exome sequencing (WES) was performed on the genomic DNA from the patient and biological mother. A heterozygous mutation in B3GAT3 (c.888+262T>G) in the invariant “GT” splice donor site was identified. This variant is considered to be pathogenic as it decreases the splicing efficiency in the mRNA. |
| format | Article |
| id | doaj-art-85aaf58fe2f4451fb982d9ab6069209c |
| institution | OA Journals |
| issn | 2090-6544 2090-6552 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Case Reports in Genetics |
| spelling | doaj-art-85aaf58fe2f4451fb982d9ab6069209c2025-08-20T02:08:54ZengWileyCase Reports in Genetics2090-65442090-65522017-01-01201710.1155/2017/39414833941483Novel Splicing Mutation in B3GAT3 Associated with Short Stature, GH Deficiency, Hypoglycaemia, Developmental Delay, and Multiple Congenital AnomaliesSamuel Bloor0Dinesh Giri1Mohammed Didi2Senthil Senniappan3School of Life Sciences, University of Liverpool, Liverpool, UKInstitute of Child Health, University of Liverpool, Liverpool, UKDepartment of Endocrinology, Alder Hey Children’s NHS Foundation Trust, Liverpool, UKInstitute of Child Health, University of Liverpool, Liverpool, UKB3GAT3, encoding β-1,3-glucuronyltransferase 3, has an important role in proteoglycan biosynthesis. Homozygous B3GAT3 mutations have been associated with short stature, skeletal deformities, and congenital heart defects. We describe for the first time a novel heterozygous splice site mutation in B3GAT3 contributing to severe short stature, growth hormone (GH) deficiency, recurrent ketotic hypoglycaemia, facial dysmorphism, and congenital heart defects. A female infant, born at 34 weeks’ gestation to nonconsanguineous Caucasian parents with a birth weight of 1.9 kg, was noted to have cloacal abnormality, ventricular septal defect, pulmonary stenosis, and congenital sensorineural deafness. At 4 years of age, she was diagnosed with GH deficiency due to her short stature (height < 2.5 SD). MRI of the pituitary gland revealed a small anterior pituitary. She has multiple dysmorphic features: anteverted nares, small upturned nose, hypertelorism, slight frontal bossing, short proximal bones, hypermobile joints, and downslanting palpebral fissures. Whole exome sequencing (WES) was performed on the genomic DNA from the patient and biological mother. A heterozygous mutation in B3GAT3 (c.888+262T>G) in the invariant “GT” splice donor site was identified. This variant is considered to be pathogenic as it decreases the splicing efficiency in the mRNA.http://dx.doi.org/10.1155/2017/3941483 |
| spellingShingle | Samuel Bloor Dinesh Giri Mohammed Didi Senthil Senniappan Novel Splicing Mutation in B3GAT3 Associated with Short Stature, GH Deficiency, Hypoglycaemia, Developmental Delay, and Multiple Congenital Anomalies Case Reports in Genetics |
| title | Novel Splicing Mutation in B3GAT3 Associated with Short Stature, GH Deficiency, Hypoglycaemia, Developmental Delay, and Multiple Congenital Anomalies |
| title_full | Novel Splicing Mutation in B3GAT3 Associated with Short Stature, GH Deficiency, Hypoglycaemia, Developmental Delay, and Multiple Congenital Anomalies |
| title_fullStr | Novel Splicing Mutation in B3GAT3 Associated with Short Stature, GH Deficiency, Hypoglycaemia, Developmental Delay, and Multiple Congenital Anomalies |
| title_full_unstemmed | Novel Splicing Mutation in B3GAT3 Associated with Short Stature, GH Deficiency, Hypoglycaemia, Developmental Delay, and Multiple Congenital Anomalies |
| title_short | Novel Splicing Mutation in B3GAT3 Associated with Short Stature, GH Deficiency, Hypoglycaemia, Developmental Delay, and Multiple Congenital Anomalies |
| title_sort | novel splicing mutation in b3gat3 associated with short stature gh deficiency hypoglycaemia developmental delay and multiple congenital anomalies |
| url | http://dx.doi.org/10.1155/2017/3941483 |
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