Low intelligence but not attention deficit hyperactivity disorder is associated with resistance to thyroid hormone caused by mutation R316H in the thyroid hormone receptor {beta} gene

Journal Article · Wed Jun 01 04:00:00 EDT 1994 · Journal of Clinical Endocrinology and Metabolism

DOI:https://doi.org/10.1210/jc.78.6.1525· OSTI ID:54469

Weiss, R E; Stein, M A; Chyna, B; Phillips, W; O`Brien, T; Gutermuth, L; Refetoff, S ^[1]; Duck, S C ^[2]

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1. Univ. of Chicago, IL (United States)
2. Northwestern Univ. Medical School/Evanston Hospital, Evanston, IL (United States)

Resistance to thyroid hormone (RTH) is a syndrome of reduced responsiveness of tissues to thyroid hormone. The clinical manifestations are variable and 46-50% of children with RTH have attention deficit hyperactivity disorder (ADD). The authors present a new family with RTH (F120) found to have a mutation R316H in the thyroid hormone receptor {beta} (TR{beta}) gene identical for that reported in an unrelated family. Assignment of the mutant allele and haplotyping based on CA repeat polymorphism were done on 16 family members. Semistructured diagnostic interviews and psychometric testing were used to determine the psychiatric diagnosis of 12 family members by examiners blinded to the genotype. Three subjects were identified to have the R316H allele as well as mildly elevated free T{sub 4} index (168 {+-} 12; normal range 77-135) and nonsuppressed TSH (4.1 {+-} 1.7 mU/L). Only 2 of the subjects with RTH were found to have ADD, while one family member homozygous for the wild type TR{beta} and normal thyroid function tests also had ADD. Unaffected family members had higher full scale intelligence quotients ({vert_bar}Q) (93 {+-} 7) than any of the 3 family members with RTH (77 {+-} 5, p = 0.006). These data do not support the genetic linkage of ADD and RTH, but do suggest that RTH is associated with lower IQ scores that may confer a high likelihood of exhibiting ADD symptoms. 20 refs., 2 figs., 2 tabs.

• OSTI ID: 54469
• Journal Information: Journal of Clinical Endocrinology and Metabolism, Journal Name: Journal of Clinical Endocrinology and Metabolism Journal Issue: 6 Vol. 78; ISSN JCEMAZ; ISSN 0021-972X
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
ETIOLOGY
GENE MUTATIONS
MENTAL DISORDERS
RECEPTORS
THYROID HORMONES