Fetal hydrops

Gene: GUSB

Green List (high evidence)

GUSB (glucuronidase beta)
EnsemblGeneIds (GRCh38): ENSG00000169919
EnsemblGeneIds (GRCh37): ENSG00000169919
OMIM: 611499, Gene2Phenotype
GUSB is in 15 panels

2 reviews

Rebecca Foulger (Genomics England curator)

Comment when marking as ready: Rated as green, and mode of inheritance complete.
Created: 19 Dec 2016, 10:41 a.m.
Comment on mode of inheritance: Kept mode of inheritance as 'biallelic/AR' because OMIM reports only homozygous or compound heterozygous mutations in GUSB for MPS7 disorder. Also, the heterozygous mutation identified in PMID:8111412 is most likely incomplete. Also Table 2 in PMID:8644704 (1996) record biallelic mutations (homozygous or compound heterozygous) for 17 patients. Plus GUSB is only listed as biallelic in other V1 panels.
Created: 19 Dec 2016, 10:40 a.m.
In a patient with nonimmune hydrops fetalis due to beta-glucuronidase deficiency (MPS7; 253220) PMID:8111412 (Vervoort et al., 1993) identified a 672C-T transition in exon 4 of the GUSB gene, resulting in a R216W substitution. The patient inherited the mutation from his father, and the mother did not carry the mutation. Currently no access to full text of this paper but from the abstract it seems that the presence of GUSB pseudogenes complicates the analysis and an additional mutation (in addition to the R216W GUSB mutation) is most likely present in the patient but as yet unidentified.
Created: 19 Dec 2016, 10:34 a.m.
Comment on list classification: Updated rating from Red to Green. One green expert review plus >3 unrelated patients from the literature that present with Mucopolysaccharidosis VII (OMIM:253220) and Fetal hydrops and contain GUSB mutations. GUSB is a confirmed DD gene for OMIM:253220.
Created: 16 Dec 2016, 11:27 a.m.
PMID:9099834 (Vervoort et al., 1997) identified 5 novel mutations in the GUSB gene in 5 MPS VII patients. Four patients presented with hydrops fetalis and 1 with an early infantile form of the disorder.
Created: 16 Dec 2016, 11:17 a.m.
Although not all mucopolysaccharidosis type VII (MPS VII) neonates present with hydrops fetalis or with related symptoms, hydrops fetalis is a common form of presentation of this mucopolysaccharidosis. PMID:8644704 (Vervoort et al., 1996) studied 17 MPS VII patients, at least 8 of which presented with Fetal hydrops. In total, in addition to 6 previously reported GUSB mutations, they detected 14 novel mutations. The mutations in hydropic fetuses were widely scattered in the GUSB gene.
Created: 16 Dec 2016, 11:15 a.m.
In a patient with severe mucopolysaccharidosis type VII (MPS7; 253220) as well as nonimmune hydrops fetalis, PMID:8111413 (Wu and Sly, 1993) identified compound heterozygosity for 2 GUSB mutations: a 1061C-T transition in exon 6 resulting in a A354V substitution, and a 1831C-T transition in exon 12 resulting in a R611W substitution.
Created: 16 Dec 2016, 11:07 a.m.
GUSB is included in the gene panel for Fetal hydrops because the phenotype of Mucopolysaccharidosis type VII storage disorder can include fetal hydrops, and the storage disorder is caused by mutations in GUSB. Note that the phenotype of Mucopolysaccharidosis type VII is highly variable, ranging from severe lethal hydrops fetalis to mild forms with survival into adulthood.
Created: 10 Oct 2016, 9:28 a.m.

Diana Wellesley (nhs)

Green List (high evidence)

Personal experience of several foetuses with hydrops and this condition
Created: 22 Nov 2016, 10:32 a.m.

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
MPS VII or Sly syndrome OMIM 253220

Publications

History Filter Activity

21 Dec 2016, Gel status: 4

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

21 December 2016. External reviews were assessed, and panel was revised according to expert review, internal discussion and additional curation. Following internal discussion, all genes from the V1.14 'RASopathies' panel were added as green EXCLUDING NF1 and SPRED1- a cautious approach was taken because Fetal hydrops is a fetal panel. All relevant genes from the 'Mucopolysaccharideosis, Gaucher, Fabry' V1.0 panel (lysosomal storage disorders) were also added to the Fetal hydrops panel as green together with genes from the literature where there is a reasonable link between the corresponding lysosomal storage disorder (LSD) and Fetal hydrops. All PEX genes from the V1.2 'Peroxisomal disorders' panel were added as green based on a link between peroxisomal biogenesis disorders and Fetal hydrops.

19 Dec 2016, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

19 Dec 2016, Gel status: 4

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for GUSB was changed to BIALLELIC, autosomal or pseudoautosomal

16 Dec 2016, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

15 Dec 2016, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene GUSB were set to Mucopolysaccharidosis VII, 253220;MPS VII (Sly syndrome); Hydrops fetalis

15 Dec 2016, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for GUSB were set to Mucopolysaccharidosis VII, 253220; MPS VII (Sly syndrome)

15 Dec 2016, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for GUSB were set to 27393412; 25305402; 24284886

10 Oct 2016, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

GUSB was added to Fetal hydropspanel. Sources: Other

10 Oct 2016, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

GUSB was created by rfoulger