Genetic linkage studies of thyroid peroxidase (TPO) gene in families with TPO deficiency

We have conducted biochemical and genetic studies in five unrelated families (denoted A, C, R, P, and G), which included nine goitrous subjects (five borderline euthyroid and four hypothyroid) with complete (n = 6) or partial (n = 3) thyroid peroxidase (TPO) deficiency. Thyroid tissue was obtained f...

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Veröffentlicht in:The journal of clinical endocrinology and metabolism Jg. 72; H. 2; S. 471
Hauptverfasser: Mangklabruks, A, Billerbeck, A E, Wajchenberg, B, Knobel, M, Cox, N J, DeGroot, L J, Medeiros-Neto, G
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 01.02.1991
Schlagworte:
Bacterial Proteins
Deoxyribonucleases, Type II Site-Specific
DNA - genetics
DNA Restriction Enzymes
Female
Genetic Linkage
Humans
Iodide Peroxidase - deficiency
Iodide Peroxidase - genetics
Iodides - metabolism
Lod Score
Male
Pedigree
Polymorphism, Restriction Fragment Length
Thyroid Gland - enzymology
Thyroid Gland - physiopathology
Thyrotropin - blood
Thyrotropin-Releasing Hormone
Thyroxine - blood
Triiodothyronine - blood
ISSN:0021-972X
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Zusammenfassung:We have conducted biochemical and genetic studies in five unrelated families (denoted A, C, R, P, and G), which included nine goitrous subjects (five borderline euthyroid and four hypothyroid) with complete (n = 6) or partial (n = 3) thyroid peroxidase (TPO) deficiency. Thyroid tissue was obtained from four subjects, respectively, in families A, C, and R. No iodide organification or iodide incorporation into protein was present in families A and C. The two affected siblings in family R had a low normal tissue thyroperoxidase activity. Using a 0.8-kilobase (kb) cDNA clone (pM5) encoding 30% of the cDNA of human TPO gene down-stream from basepair 730 and four restriction enzymes (TaqI, PstI, BglI, and BglII), we were unable to find any polymorphisms in family A. In another family (C) blood samples were obtained from only two family members, and consequently, it was not possible to determine linkage. DNA from families G, P, and C showed biallelic polymorphisms when digested with BglII, at 8.7 and 8.5 kb. In family R we detected two biallelic polymorphisms at 9.0 and 8.5 kb, and the 9.0-kb bands were clearly larger than 8.7-kb bands found in the other subjects. Also, there was an absence of a 4.0- to 3.9-kb band that may represent a partial gene deletion. With PstI-restricted DNA a possible deletion of 5.5-kb band was also present in affected siblings of family R. The logarithm of odds (Lod) score analyzed from the family with inbreeding (R) was compatible with linkage of disease and the TPO gene (Lod = 2.08). When this method was used with families G and P, the Lod score was inconsistent with linkage between disease and the TPO gene. These data suggest that the cause of TPO deficiency in these families is heterogeneous. However, the restriction fragment length polymorphism pattern of BglII-restricted DNA in the R family strongly suggests that a partial TPO gene deletion has occurred in this family.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:0021-972X
DOI:10.1210/jcem-72-2-471