Growth hormone insensitivity with immune dysfunction caused by a STAT5B mutation in the south of Brazil: evidence for a founder effect
ABSTRACT Homozygous STAT5B mutations causing growth hormone insensitivity with immune dysfunction were described in 10 patients since 2003, including two Brazilian brothers from the south of Brazil. Our objectives were to evaluate the prevalence of their STAT5B mutation in this region and to analyze...
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| Format: | Article |
| Language: | English |
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Sociedade Brasileira de Genética
2017-06-01
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| Series: | Genetics and Molecular Biology |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572017000300436&lng=en&tlng=en |
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| author | Renata C. Scalco Fernanda T. Gonçalves Hadassa C. Santos Mari M. S. G. Cardena Carlos A. Tonelli Mariana F. A. Funari Rosana M. Aracava Alexandre C. Pereira Cintia Fridman Alexander A. L. Jorge |
| author_facet | Renata C. Scalco Fernanda T. Gonçalves Hadassa C. Santos Mari M. S. G. Cardena Carlos A. Tonelli Mariana F. A. Funari Rosana M. Aracava Alexandre C. Pereira Cintia Fridman Alexander A. L. Jorge |
| author_sort | Renata C. Scalco |
| collection | DOAJ |
| description | ABSTRACT Homozygous STAT5B mutations causing growth hormone insensitivity with immune dysfunction were described in 10 patients since 2003, including two Brazilian brothers from the south of Brazil. Our objectives were to evaluate the prevalence of their STAT5B mutation in this region and to analyze the presence of a founder effect. We obtained DNA samples from 1,205 local inhabitants, 48 relatives of the homozygous patients and four individuals of another affected family. Genotyping for STAT5B c.424_427del mutation and for two polymorphic markers around it was done through fragment analysis technique. We also determined Y-chromosome and mtDNA haplotypes and genomic ancestry in heterozygous carriers. We identified seven families with STAT5B c.424_427del mutation, with 33 heterozygous individuals. The minor allelic frequency of this mutation was 0.29% in this population (confidence interval 95% 0.08-0.5%), which is significantly higher than the frequency of other pathogenic STAT5B allele variants observed in public databases (p < 0.001). All heterozygous carriers had the same haplotype present in the homozygous patients, found in only 9.4% of non-carriers (p < 0.001), supporting the existence of a founder effect. The Y-chromosome haplotype, mtDNA and genomic ancestry analysis indicated a European origin of this mutation. Our results provide compelling evidence for a founder effect of STAT5B c.424_427del mutation. |
| first_indexed | 2024-12-11T09:40:17Z |
| format | Article |
| id | doaj.art-d662dc41a14d4187960452232e373408 |
| institution | Directory Open Access Journal |
| issn | 1678-4685 |
| language | English |
| last_indexed | 2024-12-11T09:40:17Z |
| publishDate | 2017-06-01 |
| publisher | Sociedade Brasileira de Genética |
| record_format | Article |
| series | Genetics and Molecular Biology |
| spelling | doaj.art-d662dc41a14d4187960452232e3734082022-12-22T01:12:42ZengSociedade Brasileira de GenéticaGenetics and Molecular Biology1678-46852017-06-0140243644110.1590/1678-4685-gmb-2016-0231S1415-47572017000300436Growth hormone insensitivity with immune dysfunction caused by a STAT5B mutation in the south of Brazil: evidence for a founder effectRenata C. ScalcoFernanda T. GonçalvesHadassa C. SantosMari M. S. G. CardenaCarlos A. TonelliMariana F. A. FunariRosana M. AracavaAlexandre C. PereiraCintia FridmanAlexander A. L. JorgeABSTRACT Homozygous STAT5B mutations causing growth hormone insensitivity with immune dysfunction were described in 10 patients since 2003, including two Brazilian brothers from the south of Brazil. Our objectives were to evaluate the prevalence of their STAT5B mutation in this region and to analyze the presence of a founder effect. We obtained DNA samples from 1,205 local inhabitants, 48 relatives of the homozygous patients and four individuals of another affected family. Genotyping for STAT5B c.424_427del mutation and for two polymorphic markers around it was done through fragment analysis technique. We also determined Y-chromosome and mtDNA haplotypes and genomic ancestry in heterozygous carriers. We identified seven families with STAT5B c.424_427del mutation, with 33 heterozygous individuals. The minor allelic frequency of this mutation was 0.29% in this population (confidence interval 95% 0.08-0.5%), which is significantly higher than the frequency of other pathogenic STAT5B allele variants observed in public databases (p < 0.001). All heterozygous carriers had the same haplotype present in the homozygous patients, found in only 9.4% of non-carriers (p < 0.001), supporting the existence of a founder effect. The Y-chromosome haplotype, mtDNA and genomic ancestry analysis indicated a European origin of this mutation. Our results provide compelling evidence for a founder effect of STAT5B c.424_427del mutation.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572017000300436&lng=en&tlng=enfounder effectgrowth hormone insensitivityimmune dysfunctionSTAT5B |
| spellingShingle | Renata C. Scalco Fernanda T. Gonçalves Hadassa C. Santos Mari M. S. G. Cardena Carlos A. Tonelli Mariana F. A. Funari Rosana M. Aracava Alexandre C. Pereira Cintia Fridman Alexander A. L. Jorge Growth hormone insensitivity with immune dysfunction caused by a STAT5B mutation in the south of Brazil: evidence for a founder effect Genetics and Molecular Biology founder effect growth hormone insensitivity immune dysfunction STAT5B |
| title | Growth hormone insensitivity with immune dysfunction caused by a STAT5B mutation in the south of Brazil: evidence for a founder effect |
| title_full | Growth hormone insensitivity with immune dysfunction caused by a STAT5B mutation in the south of Brazil: evidence for a founder effect |
| title_fullStr | Growth hormone insensitivity with immune dysfunction caused by a STAT5B mutation in the south of Brazil: evidence for a founder effect |
| title_full_unstemmed | Growth hormone insensitivity with immune dysfunction caused by a STAT5B mutation in the south of Brazil: evidence for a founder effect |
| title_short | Growth hormone insensitivity with immune dysfunction caused by a STAT5B mutation in the south of Brazil: evidence for a founder effect |
| title_sort | growth hormone insensitivity with immune dysfunction caused by a stat5b mutation in the south of brazil evidence for a founder effect |
| topic | founder effect growth hormone insensitivity immune dysfunction STAT5B |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572017000300436&lng=en&tlng=en |
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