Adult siblings with homozygous G6PC3 mutations expand our understanding of the severe congenital neutropenia type 4 (SCN4) phenotype
Open Access
- 21 November 2012
- journal article
- case report
- Published by Springer Science and Business Media LLC in BMC Medical Genetics
- Vol. 13 (1), 111
- https://doi.org/10.1186/1471-2350-13-111
Abstract
Severe congenital neutropenia type 4 (SCN4) is an autosomal recessive disorder caused by mutations in the third subunit of the enzyme glucose-6-phosphatase (G6PC3). Its core features are congenital neutropenia and a prominent venous skin pattern, and affected individuals have variable birth defects. Oculocutaneous albinism type 4 (OCA4) is caused by autosomal recessive mutations in SLC45A2. We report a sister and brother from Newfoundland, Canada with complex phenotypes. The sister was previously reported by Cullinane et al., 2011. We performed homozygosity mapping, next generation sequencing and conventional Sanger sequencing to identify mutations that cause the phenotype in this family. We have also summarized clinical data from 49 previously reported SCN4 cases with overlapping phenotypes and interpret the medical histories of these siblings in the context of the literature. The siblings’ phenotype is due in part to a homozygous mutation in G6PC3, [c.829C > T, p.Gln277X]. Their ages are 38 and 37 years respectively and they are the oldest SCN4 patients published to date. Both presented with congenital neutropenia and later developed Crohn disease. We suggest that the latter is a previously unrecognized SCN4 manifestation and that not all affected individuals have an intellectual disability. The sister also has a homozygous mutation in SLC45A2, which explains her severe oculocutaneous hypopigmentation. Her brother carried one SLC45A2 mutation and was diagnosed with “partial OCA” in childhood. This family highlights that apparently novel syndromes can in fact be caused by two known autosomal recessive disorders.Keywords
This publication has 33 references indexed in Scilit:
- Homozygosity Mapping and Whole-Exome Sequencing to Detect SLC45A2 and G6PC3 Mutations in a Single Patient with Oculocutaneous Albinism and NeutropeniaJournal of Investigative Dermatology, 2011
- Severe congenital neutropenia resulting from G6PC3 deficiency with increased neutrophil CXCR4 expression and myelokathexisBlood, 2010
- Further delineation of the phenotype of severe congenital neutropenia type 4 due to mutations in G6PC3European Journal of Human Genetics, 2010
- Digenic mutations in severe congenital neutropeniaHaematologica, 2010
- BFAST: An Alignment Tool for Large Scale Genome ResequencingPLOS ONE, 2009
- Prevalence of mutations in ELANE, GFI1, HAX1, SBDS, WAS and G6PC3 in patients with severe congenital neutropeniaBritish Journal of Haematology, 2009
- Glucose-6-phosphatase Catalytic Subunit Gene FamilyJournal of Biological Chemistry, 2009
- HomozygosityMapper--an interactive approach to homozygosity mappingNucleic Acids Research, 2009
- A Syndrome with Congenital Neutropenia and Mutations inG6PC3New England Journal of Medicine, 2009
- Oculocutaneous Albinism Type 4 Is One of the Most Common Types of Albinism in JapanAmerican Journal of Human Genetics, 2004