Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/102837
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Type: Journal article
Title: Identification of an IGSF1-specific deletion in a five-generation pedigree with X-linked Central Hypothyroidism without macroorchidism
Author: Hughes, J.
Aubert, M.
Heatlie, J.
Gardner, A.
Gecz, J.
Morgan, T.
Belsky, J.
Thomas, P.
Citation: Clinical Endocrinology, 2016; 85(4):609-615
Publisher: Wiley-Blackwell
Issue Date: 2016
ISSN: 0300-0664
1365-2265
Statement of
Responsibility: 
James N. Hughes, Matthew Aubert, Jessica Heatlie, Alison Gardner, Jozef Gecz, Thomas Morgan, Joseph Belsky and Paul Q. Thomas
Abstract: IGSF1 deficiency syndrome (IDS) is a recently described X-linked congenital central hypothyroidism disorder characterized by loss-of-function mutations in the immunoglobulin superfamily member 1 (IGSF1) gene. The phenotypic spectrum and intrafamilial variability associated with IDS remain unclear due to a paucity of large, well-characterized pedigrees. Here, we present phenotypic analysis and molecular characterization of a five-generation pedigree with IGSF1 deficiency containing 10 affected males.Pituitary function was assessed in all available family members (n = 8 affected males and n = 5 carrier females). Molecular characterization of the family was performed by Sanger sequencing of PCR products amplified from the IGSF1 locus and by array comparative genomic hybridization.A 42-kb IGSF1 deletion spanning the entire coding sequence was identified in all affected males. TSH deficiency, although subclinical in one case, was identified in all affected males (n = 8). PRL and GH deficiency were also present in 5 of 6 and 4 of 8 affected males, respectively. In contrast to previous reports, macroorchidism was not detected in any of the four affected males who were examined for this feature. Only 1 of 5 carrier females had pituitary dysfunction (TSH and GH deficiency).Individuals with identical IGSF1 deletions can exhibit variable pituitary hormone deficiencies, of which overt TSH deficiency is the most consistent feature. We also show that macroorchidism is not obligatory in males with IDS. Mutations of IGSF1 should therefore be considered in males with isolated hypopituitarism that includes TSH deficiency.
Keywords: Humans; Hypopituitarism; Genetic Diseases, X-Linked; Immunoglobulins; Membrane Proteins; Pedigree; Sequence Deletion; Mutation; Congenital Hypothyroidism; Female; Male; Comparative Genomic Hybridization
Rights: © 2016 John Wiley & Sons Ltd.
RMID: 0030047232
DOI: 10.1111/cen.13094
Appears in Collections:Medicine publications

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