Tight linkage of the human c-erbAβ gene with the syndrome of generalized thyroid hormone resistance is present in multiple kindreds

H. G. Fein, K. D. Burman, Y. Y. Djuh, S. J. Usala, A. E. Bale, B. D. Weintraub, Robert Christian Smallridge

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Generalized thyroid hormone resistance recently was reported to map in a single kindred to the same chromosomal region as the c-erbAβ gene, which codes for a putative thyroid hormone receptor. Restriction fragment length polymorphisms (RFLPs) of c-erbAβ were linked with GTHR in three kindreds with variable neuropsychologic dysfunction; two unrelated kindreds have been reported to possess different single base mutations in the T3 binding domain of c-erbAβ. In order to ascertain if tight linkage with c-erbAβ could be generalized to other families with this syndrome, we performed RFLP analysis in a separate laboratory on an unrelated family with GTHR which lacks the neuropsychologic defects or short stature often associated with GTHR (Kindred WR). RFLPs were identified after Bam HI and Eco RV digestion of DNA from leukocytes from 14 family members. The Bam HI RFLPs were 2.8 and 5.3 kb bands, and the Eco RV RFLPs were 1.6 and 3.3 kb bands. These RFLPs cosegregated with the GTHR phenotype and 11 family members were informative when both RFLPs were employed. The logarithm of the odds ratio between GTHR and c-erbAβ was 3.67, and therefore GTHR mapped to the c-erbAβ locus in this kindred. Allelic-specific hybridization with a probe constructed to identify the C to A mutation at nucleotide position 1643 (previously identified in one other kindred) suggested that our family has a different c-erbAβ abnormality. Although GTHR appears to be commonly associated with alterations in the human c-erbAβ gene, different kindreds may inherit different genetic defects.

Original languageEnglish (US)
Pages (from-to)219-223
Number of pages5
JournalJournal of Endocrinological Investigation
Volume14
Issue number3
StatePublished - 1991
Externally publishedYes

Fingerprint

erbA Genes
Thyroid Hormone Resistance Syndrome
Restriction Fragment Length Polymorphisms
Thyroid Hormone Receptors
Mutation
Digestion
Leukocytes
Nucleotides
Odds Ratio
Phenotype

Keywords

  • linkage analysis
  • restriction fragment length polymorphisms
  • thyroid hormone receptor
  • thyroid hormone resistance

ASJC Scopus subject areas

  • Endocrinology

Cite this

Tight linkage of the human c-erbAβ gene with the syndrome of generalized thyroid hormone resistance is present in multiple kindreds. / Fein, H. G.; Burman, K. D.; Djuh, Y. Y.; Usala, S. J.; Bale, A. E.; Weintraub, B. D.; Smallridge, Robert Christian.

In: Journal of Endocrinological Investigation, Vol. 14, No. 3, 1991, p. 219-223.

Research output: Contribution to journalArticle

Fein, H. G. ; Burman, K. D. ; Djuh, Y. Y. ; Usala, S. J. ; Bale, A. E. ; Weintraub, B. D. ; Smallridge, Robert Christian. / Tight linkage of the human c-erbAβ gene with the syndrome of generalized thyroid hormone resistance is present in multiple kindreds. In: Journal of Endocrinological Investigation. 1991 ; Vol. 14, No. 3. pp. 219-223.
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abstract = "Generalized thyroid hormone resistance recently was reported to map in a single kindred to the same chromosomal region as the c-erbAβ gene, which codes for a putative thyroid hormone receptor. Restriction fragment length polymorphisms (RFLPs) of c-erbAβ were linked with GTHR in three kindreds with variable neuropsychologic dysfunction; two unrelated kindreds have been reported to possess different single base mutations in the T3 binding domain of c-erbAβ. In order to ascertain if tight linkage with c-erbAβ could be generalized to other families with this syndrome, we performed RFLP analysis in a separate laboratory on an unrelated family with GTHR which lacks the neuropsychologic defects or short stature often associated with GTHR (Kindred WR). RFLPs were identified after Bam HI and Eco RV digestion of DNA from leukocytes from 14 family members. The Bam HI RFLPs were 2.8 and 5.3 kb bands, and the Eco RV RFLPs were 1.6 and 3.3 kb bands. These RFLPs cosegregated with the GTHR phenotype and 11 family members were informative when both RFLPs were employed. The logarithm of the odds ratio between GTHR and c-erbAβ was 3.67, and therefore GTHR mapped to the c-erbAβ locus in this kindred. Allelic-specific hybridization with a probe constructed to identify the C to A mutation at nucleotide position 1643 (previously identified in one other kindred) suggested that our family has a different c-erbAβ abnormality. Although GTHR appears to be commonly associated with alterations in the human c-erbAβ gene, different kindreds may inherit different genetic defects.",
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AU - Smallridge, Robert Christian

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