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Purpose <p>Pendred syndrome (PDS) is an autosomal recessive disease caused by variants in <i>SLC26A4</i> manifesting thyroid dyshormonogenesis. Patients typically present with goiter and sensorineural hearing loss (SNHL). The prevalence of PDS in non-African populations is estimated to be between 7.5 and 10 per 100,000, while its occurrence in African populations has not been reported with molecular analysis.</p> Methods <p>This study, conducted at a university research center in Miami, USA and Khartoum, Sudan, to investigate PDS in Sudanese families with congenital hypothyroidism (CH). It involved 32 Sudanese families with children diagnosed with CH between 2016 and 2023. Patients underwent clinical evaluation, thyroid function tests, and genetic sequencing.</p> Results <p>Two disease-causing <i>SLC26A4</i> variants were identified in two consanguineous families with first-cousin parents. One homozygous nonsense variant causing premature termination, p.Trp482*, previously reported as part of a compound heterozygous defect together with p.Gly102Arg, while the other homozygous defect was a previously reported missense variant, p.Thr410Met. In 32 families (72 individuals) whole exome sequencing data revealed 56.3% of families or 45.8% individuals harbored the <i>SLC26A4</i> variants either in hetero or homozygous state. Of the 33 subjects who tested positive for the variants, 12 (36.4%) harbored more than one <i>SLC26A4</i> variant.</p> Conclusions <p><?tk 2?>This report extends our understanding of the severity of the phenotypes caused by deleterious bi-allelic variants in <i>SLC26A4</i>. Recurrent <i>SLC26A4</i> variants observed in our cohort likely reflect high consanguinity rather than a founder effect. <i>SLC26A4</i> screening could be a part of the molecular testing for children presenting with congenital or early-onset SNHL in Sudan.</p>

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Prevalence of pendrin defects in sudanese families with congenital hypothyroidism

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月16日

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  • Mohammad S. Islam,
  • Alexandra M. Dumitrescu,
  • Amna Ahmed,
  • Samuel Refetoff,
  • Roy E. Weiss

摘要

Purpose

Pendred syndrome (PDS) is an autosomal recessive disease caused by variants in SLC26A4 manifesting thyroid dyshormonogenesis. Patients typically present with goiter and sensorineural hearing loss (SNHL). The prevalence of PDS in non-African populations is estimated to be between 7.5 and 10 per 100,000, while its occurrence in African populations has not been reported with molecular analysis.

Methods

This study, conducted at a university research center in Miami, USA and Khartoum, Sudan, to investigate PDS in Sudanese families with congenital hypothyroidism (CH). It involved 32 Sudanese families with children diagnosed with CH between 2016 and 2023. Patients underwent clinical evaluation, thyroid function tests, and genetic sequencing.

Results

Two disease-causing SLC26A4 variants were identified in two consanguineous families with first-cousin parents. One homozygous nonsense variant causing premature termination, p.Trp482*, previously reported as part of a compound heterozygous defect together with p.Gly102Arg, while the other homozygous defect was a previously reported missense variant, p.Thr410Met. In 32 families (72 individuals) whole exome sequencing data revealed 56.3% of families or 45.8% individuals harbored the SLC26A4 variants either in hetero or homozygous state. Of the 33 subjects who tested positive for the variants, 12 (36.4%) harbored more than one SLC26A4 variant.

Conclusions

This report extends our understanding of the severity of the phenotypes caused by deleterious bi-allelic variants in SLC26A4. Recurrent SLC26A4 variants observed in our cohort likely reflect high consanguinity rather than a founder effect. SLC26A4 screening could be a part of the molecular testing for children presenting with congenital or early-onset SNHL in Sudan.