Identification novel mutations and phenotypic spectrum expanding in PATL2 in infertile women with IVF/ICSI failure.
J Assist Reprod Genet
; 41(5): 1233-1243, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38536595
ABSTRACT
AIM:
Abnormalities in oocyte maturation, fertilization, and early embryonic development are major causes of primary infertility in women who are undergoing IVF/ICSI attempts. Although many genetic factors responsible for these abnormal phenotypes have been identified, there are more additional pathogenic genes and variants yet to be discovered. Previous studies confirmed that bi-allelic PATL2 deficiency is an important factor for female infertility. In this study, 935 infertile patients with IVF/ICSI failure were selected for whole-exome sequencing, and 18 probands carrying PATL2 variants with a recessive inheritance pattern were identified.METHODS:
We estimated that the prevalence contributed by PATL2 was 1.93% (18/935) in our study cohort.RESULTS:
15 novel variants were found in those families, including c.1093C > T, c.1609dupA, c.1204C > T, c.643dupG, c.877-2A > G, c.1228C > G, c.925G > A, c.958G > A, c.4A > G, c.1258T > C, c.1337G > A, c.1264dupA, c.88G > T, c.1065-2A > G, and c.1271T > C. The amino acids altered by the corresponding variants were highly conserved in mammals, and in silico analysis and 3D molecular modeling suggested that the PATL2 mutants impaired the physiologic function of the resulting proteins. Diverse clinical phenotypes, including oocyte maturation defect, fertilization failure, and early embryonic arrest might result from different variants of PATL2.CONCLUSIONS:
These results expand the spectrum of PATL2 variants and provide an important reference for genetic counseling for female infertility, and they increase our understanding of the mechanisms of oocyte maturation arrest caused by PATL2 deficiency.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fenótipo
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Proteínas Nucleares
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Fertilização in vitro
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Proteínas de Ligação a RNA
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Injeções de Esperma Intracitoplásmicas
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Sequenciamento do Exoma
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Infertilidade Feminina
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Mutação
Limite:
Adult
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Female
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Humans
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Pregnancy
Idioma:
En
Revista:
J Assist Reprod Genet
Assunto da revista:
GENETICA
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MEDICINA REPRODUTIVA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China