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Mutations in SLC29a3, encoding an equilibrative nucleoside transporter ENT3, cause a familial histiocytosis syndrome (Faisalabad histiocytosis) and familial Rosai-Dorfman disease
Morgan, NV Morris, MR Cangul, H Gleeson, D Straatman-Iwanowska, A Davies, N Keenan, S Pasha, S Rahman, F Gentle, D
Morgan, NV
Morris, MR
Cangul, H
Gleeson, D
Straatman-Iwanowska, A
Davies, N
Keenan, S
Pasha, S
Rahman, F
Gentle, D
Editors
Other contributors
Affiliation
Epub Date
Issue Date
2010-02-05
Submitted date
Subjects
Cell Line, Tumor
Chromosomes, Human, Pair 10
Animals
Humans
Mice
Breast Neoplasms
Histiocytosis, Sinus
Syndrome
Nucleoside Transport Proteins
RNA, Small Interfering
Colony-Forming Units Assay
Physical Chromosome Mapping
DNA Mutational Analysis
Family
Cell Proliferation
Gene Expression Regulation
Base Sequence
Mutation
Alleles
Molecular Sequence Data
Female
Urinary Bladder Neoplasms
Embryo, Mammalian
Genetic Loci
Chromosomes, Human, Pair 10
Animals
Humans
Mice
Breast Neoplasms
Histiocytosis, Sinus
Syndrome
Nucleoside Transport Proteins
RNA, Small Interfering
Colony-Forming Units Assay
Physical Chromosome Mapping
DNA Mutational Analysis
Family
Cell Proliferation
Gene Expression Regulation
Base Sequence
Mutation
Alleles
Molecular Sequence Data
Female
Urinary Bladder Neoplasms
Embryo, Mammalian
Genetic Loci
Alternative
Abstract
The histiocytoses are a heterogeneous group of disorders characterised by an excessive number of histiocytes. In most cases the pathophysiology is unclear and treatment is nonspecific. Faisalabad histiocytosis (FHC) (MIM 602782) has been classed as an autosomal recessively inherited form of histiocytosis with similarities to Rosai-Dorfman disease (RDD) (also known as sinus histiocytosis with massive lymphadenopathy (SHML)). To elucidate the molecular basis of FHC, we performed autozygosity mapping studies in a large consanguineous family and identified a novel locus at chromosome 10q22.1. Mutation analysis of candidate genes within the target interval identified biallelic germline mutations in SLC29A3 in the FHC kindred and in two families reported to have familial RDD. Analysis of SLC29A3 expression during mouse embryogenesis revealed widespread expression by e14.5 with prominent expression in the central nervous system, eye, inner ear, and epithelial tissues including the gastrointestinal tract. SLC29A3 encodes an intracellular equilibrative nucleoside transporter (hENT3) with affinity for adenosine. Recently germline mutations in SLC29A3 were also described in two rare autosomal recessive disorders with overlapping phenotypes: (a) H syndrome (MIM 612391) that is characterised by cutaneous hyperpigmentation and hypertrichosis, hepatomegaly, heart anomalies, hearing loss, and hypogonadism; and (b) PHID (pigmented hypertrichosis with insulin-dependent diabetes mellitus) syndrome. Our findings suggest that a variety of clinical diagnoses (H and PHID syndromes, FHC, and familial RDD) can be included in a new diagnostic category of SLC29A3 spectrum disorder. © 2010 Morgan et al.
Citation
Morgan, N. V., Morris, M. R., Cangul, H., Gleeson, D., Straatman-Iwanowska, A., Davies, N., Keenan, S., Pasha, S., Rahman, F. et al. (2010) Mutations in SLC29a3, encoding an equilibrative nucleoside transporter ENT3, cause a familial histiocytosis syndrome (Faisalabad histiocytosis) and familial Rosai-Dorfman disease, PLoS Genetics, 6(2), e1000833.
Publisher
Journal
Research Unit
PubMed ID
20140240
PubMed Central ID
Embedded videos
Type
Journal article
Language
en
Description
Series/Report no.
ISSN
EISSN
1553-7404
ISBN
ISMN
Gov't Doc #
Sponsors
WellChild, the Wellcome Trust, and Cancer Research UK for financial support.
HC was supported by grants from EMBO (ASTF 121.00-2007) and ESF (Frontiers of Functional Genomics, Exchange Grant 2008)
Rights
Licence for published version: Creative Commons Attribution 4.0 International