A Novel Pathogenic Variant in PAX8 Leads to Familial Congenital Hypothyroidism

We report a 10-month-old girl with familial congenital hypothyroidism harboring a novel heterozygous pathogenic variant in the paired DNA-binding domain of (NM_003466:c.110T>C:p.Leu37Pro). Genotype-phenotype correlation revealed complete penetrance of this defect in this family, in which the affe...

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Bibliographic Details
Published inThyroid (New York, N.Y.) Vol. 32; no. 8; p. 1000
Main Authors França, Monica Malheiros, Reeve, Lucy, Dumitrescu, Alexandra M, de Bock, Martin, Refetoff, Samuel
Format Journal Article
LanguageEnglish
Published United States 01.08.2022
Subjects
Congenital Hypothyroidism - genetics
Female
Humans
Infant
Male
Mutation
Paired Box Transcription Factors - genetics
Paired Box Transcription Factors - metabolism
PAX8 Transcription Factor - genetics
Thyroid Dysgenesis - genetics
PAX8
pathogenic variant
congenital hypothyroidism
paired DNA-binding domain
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Summary:We report a 10-month-old girl with familial congenital hypothyroidism harboring a novel heterozygous pathogenic variant in the paired DNA-binding domain of (NM_003466:c.110T>C:p.Leu37Pro). Genotype-phenotype correlation revealed complete penetrance of this defect in this family, in which the affected father and half-brother carry the same mutation. This deleterious variant has not been reported in any of the available databases [MAFgnomAD = 0, dbSNP (-)], and the amino acid leucine at position 37 is highly conserved across species. Establishing the molecular diagnosis expands our knowledge on the cause of thyroid dysgenesis and provides a guide for counseling and early treatment.
ISSN:1557-9077
DOI:10.1089/thy.2022.0117