Otic Lesions and Congenital Hypothyroidism in the Developing Chick*

Bargman, Gerald J.; Gardner, Lytt I.

doi:10.1172/jci105673

Cited by 24 publications

(3 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most cases of deafness in CH are secondary, caused by the lack of thyroid hormones that are necessary for the normal development of the peripheral and central auditory system [17]. This is in agreement with histological findings in CH animals, where an immature development of the organ of Corti, including hair cells and tectorial membrane, has been observed [4,31]. However, sensorineural hearing loss developing in children with CH due to dyshormonogenesis may also be a manifestation of Pendred syndrome.…”

Section: Mutations In Pds/slc26a4 As a Cause Of Deafness In Chsupporting

confidence: 85%

Pendred syndrome among patients with congenital hypothyroidism detected by neonatalscreening: identification of two novel PDS/SLC26A4 mutations

et al. 2007

View full text Add to dashboard Cite

Pendred syndrome is an autosomal recessive disorder characterised by sensorineural hearing loss and thyroid dyshormonogenesis. It is caused by mutations in the PDS/SLC26A4 gene (OMIM 605646) encoding for pendrin. Hypothyroidism in Pendred syndrome can be--although rarely--present from birth and therefore diagnosed by neonatal screening. The aim of our study was to identify patients with Pendred syndrome among a historical cohort of patients with congenital hypothyroidism (CH) identified by neonatal screening, and to find their mutations in the PDS/SLC26A4 gene. We investigated 197 Czech Caucasian children with CH detected by the neonatal screening between the years 1985 and 2005. The clinical diagnosis of Pendred syndrome was based on the laboratory and sonographic signs of thyroid dyshormonogenesis in association with sensorineural hearing loss. In subjects clinically diagnosed with Pendred syndrome, we sequenced all exons and exon-intron boundaries of the PDS/SLC26A4 gene. Hearing loss was present in 10/197 children with screening-detected CH. Of these, three fulfilled the diagnostic criteria of Pendred syndrome. Two patients were compound heterozygotes for PDS/SLC26A4 mutations: patient 1 carried c.2089+1G>A / c.3G>C and patient 2 carried p.Tyr530His / p.Val422Asp. Two of the four identified mutations were novel (c.3G>C in patient 1 and p.Val422Asp in patient 2). The third patient was free of mutations in the PDS/SLC26A4 gene, representing a phenocopy. In conclusion, our results indicate the rarity of Pendred syndrome as a cause of CH. The identification of two novel mutations expands the spectrum of mutations in the PDS/SLC26A4 gene and emphasizes their marked allelic heterogeneity.

show abstract

Section: Mutations In Pds/slc26a4 As a Cause Of Deafness In Chsupporting

confidence: 85%

Pendred syndrome among patients with congenital hypothyroidism detected by neonatalscreening: identification of two novel PDS/SLC26A4 mutations

et al. 2007

View full text Add to dashboard Cite

show abstract

“…The object of the present investigation was to find out by means of induced hypothyroidism in mice whether deafness could be caused by hypothyroidism, and, in the event of 235 affirmative results, to define the anatomical basis of resulting deafness as well as to see if it could be ameliorated by methods that might be applicable to man. Similar experiments were done by Bargman and Gardner (1967) on chick embryos, and abnormalities of the hair cells in the cochlea were found; but the value of these experiments is rather limited, because not only are the modes of gestation and the structure of the organ of hearing quite different in the chick and man, but there is no reference to hearing and the hypothyroid birds all died within 5 days of hatching. The experiments reported here are free of these drawbacks.…”

mentioning

confidence: 72%

An Experimental Approach to the Understanding and Treatment of Hereditary Syndromes with Congenital Deafness and Hypothyroidism

Deol

1973

Journal of Medical Genetics

125

View full text Add to dashboard Cite

Summary. Hereditary syndromes with congenital deafness and hypothyroidism have been reported from many countries. The large majority of them are believed to form a single genetic entity, known as Pendred's syndrome, and inherited as a recessive trait. The anatomical basis of deafness is not known. It is generally believed that deafness and hypothyroidism are not causally related, but are independent effects of the gene. The object of this investigation was to test this view by means ofinduced hypothyroidism. Mice from the inbred strain C57BL/Gr were given 0-1% propylthiouracil (PTU) in drinking water, and their offspring were examined. They were found to be practically deaf, and to have serious abnormalities in the inner ear. Addition of thyroxine to the drinking water containing PTU resulted in normal hearing and a normal inner ear, showing that the abnormalities were not caused by PTU as such, but were the consequence ofits inhibitory effect on thyroid function. It is, therefore, highly probable that in Pendred's syndrome and other similar conditions the loss of hearing is secondary to hypothyroidism during fetal life. Suggestions are put forward for mitigating the expressions of these syndromes by treatment with thyroxine during certain stages of development.Hereditary deafness associated with hypothyroidism has been observed in a large number of families in many countries (full references in Fraser, 1965;McKusick, 1971). As the clinical features vary a good deal, it is not possible to say how many distinct genetic entities are involved, but the large majority of these families are similar enough to be regarded as having the same syndrome. Fraser, Morgans, and Trotter (1960) have named it Pendred's syndrome, after Vaughan Pendred who first described it in 1896. Fraser (1965) has shown that it is inherited as a recessive trait, although some minor effects of the gene may be detectable in the heterozygote. He gives the frequency of affected persons in the British Isles as 0 000,075, frequency of the mutant gene causing it as 0-008, and the mutation rate as 56 per million loci per generation. Batsakis and Nishiyama (1962) have estimated that this syndrome accounts for 1 to 10%' of all hereditary deafness.

show abstract

“…Again, how much thyroid supply is needed, we do not know. Recent experiments in chickens (Bargman and Gardner, 1967) and in mice (Deol, 1973) on inner ear development also have demonstrated the necessity of adequate thyroid supply for normal development.…”

Section: The Definition Of Endemic Cretinismmentioning

confidence: 99%

Endemic cretinism—a continuous personal educational experience during 10 years

Querido

1975

Postgraduate Medical Journal

View full text Add to dashboard Cite

The processes involved in the progress of scientific knowledge have fascinated philosophers, scientific workers and non-scientists. Kuhn (1970), in his interesting essay on the structure of scientific revolutions, sees the road which the growth of scientific knowledge follows, not marked by discoveries but by what he names paradigms, ‘theories that gain their status because they are more successful than their competitors in solving a few problems …’ which are recognized as acute. Examples of paradigms in biology are, e.g. Berthold’s conceptualization of endocrinology in 1849; Mendel’s theory of inheritance; Medawar’s concept of immunological tolerance, etc.

show abstract

Otic Lesions and Congenital Hypothyroidism in the Developing Chick*

Cited by 24 publications

References 19 publications

Pendred syndrome among patients with congenital hypothyroidism detected by neonatalscreening: identification of two novel PDS/SLC26A4 mutations

Pendred syndrome among patients with congenital hypothyroidism detected by neonatalscreening: identification of two novel PDS/SLC26A4 mutations

An Experimental Approach to the Understanding and Treatment of Hereditary Syndromes with Congenital Deafness and Hypothyroidism

Endemic cretinism—a continuous personal educational experience during 10 years

Contact Info

Product

Resources

About