Heterogeneity of the growth phenotype and birth size in acid-labile subunit (ALS) deficiency
Heterogeneity of the growth phenotype and birth size in acid-labile subunit (ALS) deficiency
Purpose: the IGFALS gene encodes the acid-labile subunit (ALS) protein, which regulates circulating IGF-1. Human IGFALS mutations cause growth hormone insensitivity (GHI) associated with ALS, IGF-1 and IGFBP-3 deficiencies and mild to moderate postnatal growth impairment (height SDS ?2 to ?4). Prenatal growth impairment is not a recognised feature of this disorder, but heterozygous carriers may show an intermediate phenotype.
Methods: we report a family of five subjects, including three children born small for gestational age, who were investigated for IGFALS gene mutations.
Results: the proband, an 8.7 years female with pre- and postnatal growth failure (BW SDS ?3.04, Ht SDS ?3.86) and biochemical features of GHI, had a homozygous mutation of IGFALS, c.401T>A; p.L134Q. Her 6.1 years brother (BW SDS ?2.11, Ht SDS ?2.0) had the same homozygous IGFALS mutation. Both parents [adult height SDS ?1.76 (father) and ?1.82 (mother)] and her 2.7 years sister (BW SDS ?2.60, Ht SDS ?2.04) were heterozygous for the IGFALS mutation.
Conclusion: significant phenotypic heterogeneity was observed between family members, in particular varying degrees of prenatal growth retardation were present in the three siblings, which may have contributed to the variation in the postnatal growth phenotype
407-412
Storr, H.L.
b0f3d83e-e10a-4df4-8572-00dfe60946fc
Prasad, R.
ba7bf977-537b-4b45-9c7c-12024643c38f
Temple, I.Karen
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Metherell, L.A.
0b80ae3e-28a8-4126-9380-5ad9515c28f8
Savage, M.O.
d43e523c-054b-4cc4-9500-11d5dd5f2900
Walker, J. .
0960a6aa-7ebf-4fda-a9a4-374f0d5f4d8a
April 2015
Storr, H.L.
b0f3d83e-e10a-4df4-8572-00dfe60946fc
Prasad, R.
ba7bf977-537b-4b45-9c7c-12024643c38f
Temple, I.Karen
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Metherell, L.A.
0b80ae3e-28a8-4126-9380-5ad9515c28f8
Savage, M.O.
d43e523c-054b-4cc4-9500-11d5dd5f2900
Walker, J. .
0960a6aa-7ebf-4fda-a9a4-374f0d5f4d8a
Storr, H.L., Prasad, R., Temple, I.Karen, Metherell, L.A., Savage, M.O. and Walker, J. .
(2015)
Heterogeneity of the growth phenotype and birth size in acid-labile subunit (ALS) deficiency.
Journal of Endocrinological Investigation, 38 (4), .
(doi:10.1007/s40618-014-0195-1).
(PMID:25352235)
Abstract
Purpose: the IGFALS gene encodes the acid-labile subunit (ALS) protein, which regulates circulating IGF-1. Human IGFALS mutations cause growth hormone insensitivity (GHI) associated with ALS, IGF-1 and IGFBP-3 deficiencies and mild to moderate postnatal growth impairment (height SDS ?2 to ?4). Prenatal growth impairment is not a recognised feature of this disorder, but heterozygous carriers may show an intermediate phenotype.
Methods: we report a family of five subjects, including three children born small for gestational age, who were investigated for IGFALS gene mutations.
Results: the proband, an 8.7 years female with pre- and postnatal growth failure (BW SDS ?3.04, Ht SDS ?3.86) and biochemical features of GHI, had a homozygous mutation of IGFALS, c.401T>A; p.L134Q. Her 6.1 years brother (BW SDS ?2.11, Ht SDS ?2.0) had the same homozygous IGFALS mutation. Both parents [adult height SDS ?1.76 (father) and ?1.82 (mother)] and her 2.7 years sister (BW SDS ?2.60, Ht SDS ?2.04) were heterozygous for the IGFALS mutation.
Conclusion: significant phenotypic heterogeneity was observed between family members, in particular varying degrees of prenatal growth retardation were present in the three siblings, which may have contributed to the variation in the postnatal growth phenotype
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e-pub ahead of print date: 29 October 2014
Published date: April 2015
Organisations:
Human Development & Health
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Local EPrints ID: 371782
URI: http://eprints.soton.ac.uk/id/eprint/371782
ISSN: 1720-8386
PURE UUID: f50b8ad8-2dc3-42c8-aacd-e545503943e8
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Date deposited: 17 Nov 2014 14:13
Last modified: 15 Mar 2024 03:00
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Author:
H.L. Storr
Author:
R. Prasad
Author:
L.A. Metherell
Author:
M.O. Savage
Author:
J. . Walker
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