RESUMO
Loss-of-function DCAF17 variants cause hypogonadism, partial alopecia, diabetes mellitus, mental retardation, and deafness with variable clinical presentation. DCAF17 pathogenic variants have been largely reported in the Middle Eastern populations, but the incidence in American families is rare and animal models are lacking. Exome sequencing in 5 women with syndromic hypergonadotropic hypogonadism from 2 unrelated families revealed novel pathogenic variants in the DCAF17 gene. DCAF17 exon 2 (c.127-1G > C) novel homozygous variants were discovered in 4 Turkish siblings, while 1 American was compound heterozygous for 1-stop gain variant in exon 5 (c.C535T; p.Gln179*) and previously described stop gain variant in exon 9 (c.G906A; p.Trp302*). A mouse model mimicking loss of function in exon 2 of Dcaf17 was generated using CRISPR/Cas9 and showed female subfertility and male infertility. Our results identify 2 novel variants, and show that Dcaf17 plays a significant role in mammalian gonadal development and infertility.
Assuntos
Predisposição Genética para Doença , Infertilidade Feminina/genética , Infertilidade Masculina/genética , Proteínas Nucleares/genética , Complexos Ubiquitina-Proteína Ligase/genética , Adulto , Animais , Consanguinidade , Modelos Animais de Doenças , Exoma/genética , Feminino , Homozigoto , Humanos , Infertilidade Feminina/fisiopatologia , Infertilidade Masculina/fisiopatologia , Mutação com Perda de Função/genética , Masculino , Camundongos , Linhagem , Turquia , Estados Unidos , Sequenciamento do ExomaRESUMO
We describe the first case of trisomy 22 resulting from a monocentric, possible isochromosome 22. The female infant had multiple anomalies including an abnormal face, ambiguous genitalia, and both ventricular and atrial septal defects. Survival was short.
Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 22/genética , Face/anormalidades , Genitália Feminina/anormalidades , Comunicação Interatrial/genética , Comunicação Interventricular/genética , Isocromossomos/genética , Trissomia/genética , Adulto , Face/diagnóstico por imagem , Feminino , Genitália Feminina/diagnóstico por imagem , Transtornos do Crescimento/genética , Humanos , Recém-Nascido , Cariotipagem , Masculino , Monossomia , Fenótipo , Gravidez , Complicações na Gravidez , UltrassonografiaRESUMO
An insulin dependent diabetic patient was resistant to all but central venous insulin administration. For this reason plasma exchange was tried and it restored insulin responsiveness. An anti-insulin IgG antibody was identified in the patient's plasma. Plasma exchange reduced antibody levels and these correlated with daily insulin requirements. Kinetic analysis of anti-insulin antibodies, however caused us to doubt that they were the sole cause of the problem. Although the mechanism remains unclear, plasmapheresis proved to be an effective method of treating this patient's insulin resistance.
