Linkage of familial dysalbuminemic hyperthyroxinemia to the albumin gene in a large Amish kindred

Roy E Weiss, T. Sunthornthepvarakul, P. Angkeow, D. Marcus-Bagley, N. Cox, C. A. Alper, S. Refetoff

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Familial dysalbuminemic hyperthyroxinemia (FDH) is the most common cause of inherited euthyroid hyperthyroxinemia in Caucasians. Transmitted as an autosomal dominant trait, it is always associated with high serum total T4 (TT4) and more rarely with elevated total T3 (TT3) and/or rT3 (TrT3) concentrations. Free T4, by dialysis, and TSH levels are normal, suggesting the presence of a T4-binding protein abnormality. The abnormal serum T4 carrier shares some physical and immunological properties with albumin, suggesting that it may be albumin itself. Here we show linkage between FDH and the albumin gene in a large Amish family of Swiss descent, using as markers a SacI polymorphism in the coding sequence of the albumin gene and the group-specific component (Gc) gene, located less than 1 centimorgan from the albumin gene. Blood samples were obtained from 160 members of this kindred, and 22 had FDH identified by the pattern of T4 binding to serum proteins separated by isoelectric focusing. Serum TT4 values were above the normal range in all subjects expressing the FDH phenotype, and TrT3 levels were above the normal range in only one half. TT4 concentrations correlated positively with TrT3 and TT3. All TT3 values were, however, within the normal range. Free T4 and TSH levels were normal, confirming the euthyroid state in these subjects. FDH was associated with the albumin SacI(+)/Gc 1S haplotype, yielding a LOD (logarithm of the odds ratio) score of 5.53, with a recombination frequency of 0. These data provide strong support that a variant albumin is the cause of FDH in this kindred.

Original languageEnglish (US)
Pages (from-to)116-121
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume80
Issue number1
StatePublished - 1995
Externally publishedYes

Fingerprint

Familial Dysalbuminemic Hyperthyroxinemia
Amish
Albumins
Genes
Reference Values
Hyperthyroxinemia
Serum
Gene Components
Dialysis
Isoelectric Focusing
Polymorphism
Haplotypes
Genetic Recombination
Blood Proteins
Carrier Proteins
Blood
Odds Ratio
Phenotype

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Weiss, R. E., Sunthornthepvarakul, T., Angkeow, P., Marcus-Bagley, D., Cox, N., Alper, C. A., & Refetoff, S. (1995). Linkage of familial dysalbuminemic hyperthyroxinemia to the albumin gene in a large Amish kindred. Journal of Clinical Endocrinology and Metabolism, 80(1), 116-121.

Linkage of familial dysalbuminemic hyperthyroxinemia to the albumin gene in a large Amish kindred. / Weiss, Roy E; Sunthornthepvarakul, T.; Angkeow, P.; Marcus-Bagley, D.; Cox, N.; Alper, C. A.; Refetoff, S.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 80, No. 1, 1995, p. 116-121.

Research output: Contribution to journalArticle

Weiss, RE, Sunthornthepvarakul, T, Angkeow, P, Marcus-Bagley, D, Cox, N, Alper, CA & Refetoff, S 1995, 'Linkage of familial dysalbuminemic hyperthyroxinemia to the albumin gene in a large Amish kindred', Journal of Clinical Endocrinology and Metabolism, vol. 80, no. 1, pp. 116-121.
Weiss, Roy E ; Sunthornthepvarakul, T. ; Angkeow, P. ; Marcus-Bagley, D. ; Cox, N. ; Alper, C. A. ; Refetoff, S. / Linkage of familial dysalbuminemic hyperthyroxinemia to the albumin gene in a large Amish kindred. In: Journal of Clinical Endocrinology and Metabolism. 1995 ; Vol. 80, No. 1. pp. 116-121.
@article{7962d716644e474ba1b0accf1b1e81e7,
title = "Linkage of familial dysalbuminemic hyperthyroxinemia to the albumin gene in a large Amish kindred",
abstract = "Familial dysalbuminemic hyperthyroxinemia (FDH) is the most common cause of inherited euthyroid hyperthyroxinemia in Caucasians. Transmitted as an autosomal dominant trait, it is always associated with high serum total T4 (TT4) and more rarely with elevated total T3 (TT3) and/or rT3 (TrT3) concentrations. Free T4, by dialysis, and TSH levels are normal, suggesting the presence of a T4-binding protein abnormality. The abnormal serum T4 carrier shares some physical and immunological properties with albumin, suggesting that it may be albumin itself. Here we show linkage between FDH and the albumin gene in a large Amish family of Swiss descent, using as markers a SacI polymorphism in the coding sequence of the albumin gene and the group-specific component (Gc) gene, located less than 1 centimorgan from the albumin gene. Blood samples were obtained from 160 members of this kindred, and 22 had FDH identified by the pattern of T4 binding to serum proteins separated by isoelectric focusing. Serum TT4 values were above the normal range in all subjects expressing the FDH phenotype, and TrT3 levels were above the normal range in only one half. TT4 concentrations correlated positively with TrT3 and TT3. All TT3 values were, however, within the normal range. Free T4 and TSH levels were normal, confirming the euthyroid state in these subjects. FDH was associated with the albumin SacI(+)/Gc 1S haplotype, yielding a LOD (logarithm of the odds ratio) score of 5.53, with a recombination frequency of 0. These data provide strong support that a variant albumin is the cause of FDH in this kindred.",
author = "Weiss, {Roy E} and T. Sunthornthepvarakul and P. Angkeow and D. Marcus-Bagley and N. Cox and Alper, {C. A.} and S. Refetoff",
year = "1995",
language = "English (US)",
volume = "80",
pages = "116--121",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "1",

}

TY - JOUR

T1 - Linkage of familial dysalbuminemic hyperthyroxinemia to the albumin gene in a large Amish kindred

AU - Weiss, Roy E

AU - Sunthornthepvarakul, T.

AU - Angkeow, P.

AU - Marcus-Bagley, D.

AU - Cox, N.

AU - Alper, C. A.

AU - Refetoff, S.

PY - 1995

Y1 - 1995

N2 - Familial dysalbuminemic hyperthyroxinemia (FDH) is the most common cause of inherited euthyroid hyperthyroxinemia in Caucasians. Transmitted as an autosomal dominant trait, it is always associated with high serum total T4 (TT4) and more rarely with elevated total T3 (TT3) and/or rT3 (TrT3) concentrations. Free T4, by dialysis, and TSH levels are normal, suggesting the presence of a T4-binding protein abnormality. The abnormal serum T4 carrier shares some physical and immunological properties with albumin, suggesting that it may be albumin itself. Here we show linkage between FDH and the albumin gene in a large Amish family of Swiss descent, using as markers a SacI polymorphism in the coding sequence of the albumin gene and the group-specific component (Gc) gene, located less than 1 centimorgan from the albumin gene. Blood samples were obtained from 160 members of this kindred, and 22 had FDH identified by the pattern of T4 binding to serum proteins separated by isoelectric focusing. Serum TT4 values were above the normal range in all subjects expressing the FDH phenotype, and TrT3 levels were above the normal range in only one half. TT4 concentrations correlated positively with TrT3 and TT3. All TT3 values were, however, within the normal range. Free T4 and TSH levels were normal, confirming the euthyroid state in these subjects. FDH was associated with the albumin SacI(+)/Gc 1S haplotype, yielding a LOD (logarithm of the odds ratio) score of 5.53, with a recombination frequency of 0. These data provide strong support that a variant albumin is the cause of FDH in this kindred.

AB - Familial dysalbuminemic hyperthyroxinemia (FDH) is the most common cause of inherited euthyroid hyperthyroxinemia in Caucasians. Transmitted as an autosomal dominant trait, it is always associated with high serum total T4 (TT4) and more rarely with elevated total T3 (TT3) and/or rT3 (TrT3) concentrations. Free T4, by dialysis, and TSH levels are normal, suggesting the presence of a T4-binding protein abnormality. The abnormal serum T4 carrier shares some physical and immunological properties with albumin, suggesting that it may be albumin itself. Here we show linkage between FDH and the albumin gene in a large Amish family of Swiss descent, using as markers a SacI polymorphism in the coding sequence of the albumin gene and the group-specific component (Gc) gene, located less than 1 centimorgan from the albumin gene. Blood samples were obtained from 160 members of this kindred, and 22 had FDH identified by the pattern of T4 binding to serum proteins separated by isoelectric focusing. Serum TT4 values were above the normal range in all subjects expressing the FDH phenotype, and TrT3 levels were above the normal range in only one half. TT4 concentrations correlated positively with TrT3 and TT3. All TT3 values were, however, within the normal range. Free T4 and TSH levels were normal, confirming the euthyroid state in these subjects. FDH was associated with the albumin SacI(+)/Gc 1S haplotype, yielding a LOD (logarithm of the odds ratio) score of 5.53, with a recombination frequency of 0. These data provide strong support that a variant albumin is the cause of FDH in this kindred.

UR - http://www.scopus.com/inward/record.url?scp=0028847537&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028847537&partnerID=8YFLogxK

M3 - Article

VL - 80

SP - 116

EP - 121

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 1

ER -