Trastornos KAT6B: enterrando los síndromes Say-Barber-Biesecker-Young-Simpson y genitopatelar / The KAT6B-related disorders: Burying Say-Barber-Biesecker-Young-Simpson and genitopatellar syndrome

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Neurofibromatosis type I: mutation spectrum of NF1 in spanish patients.

Neurofibromatosis type I (NF1) is one of the most common genetic disorders in humans. NF1, a tumor predisposition syndrome, is caused by heterozygous pathogenic variants in the NF1 gene. Molecular genetic testing of NF1 is complex, especially because of the presence of a high number of partial pseudogenes, some of them with a high percentage of sequence identity. In this study, we have analyzed the largest cohort of NF1 Spanish patients (150 unrelated individuals suspected of having NF1 and 53 relatives, making a total of 203 individuals). Mutation analysis of the entire coding region was performed in all unrelated index patients. Additionally, the Multiplex Ligation-dependent Probe Amplification (MLPA) test of the NF1 gene and SPRED1 gene analysis (sequencing and MLPA test) was performed in some of the negative patients for NF1 point mutations. When fulfilling the National Institutes of Health (NIH) criterion for the clinical diagnosis of NF1, the detection rate was 79%. Among the 80 genetically confirmed NF1 probands, we detected 69 different pathogenic variants. Two mutations (3%) were gross deletions of the whole gene, the remaining 78 mutations (97%) were small changes spread among all NF1 exons. Among these 69 different mutations detected, 42 mutations were described elsewhere, and 27 mutations were novel mutations. When segregation was studied, 67% of mutations resulted de novo variants. No genetic mosaicism was detected on patients' parents.

Neuropatía óptica de Leber: utilidad de la secuenciación masiva en el estudio de mutaciones mitocondriales en aparente homoplasmia / Leber hereditary optic neuropathy: Usefulness of next generation sequencing to study mitochondrial mutations on apparent homoplasmy

Fundamento y objetivo: La neuropatía óptica hereditaria de Leber se caracteriza por una pérdida de visión aguda o subaguda, producida por mutaciones en el ADN mitocondrial. Pacientes y métodos: Presentamos el estudio molecular realizado en una familia en la que solo uno de sus miembros presentaba signos de la enfermedad. Resultados: En el caso índice y en la madre se detectó la mutación m.11778G>A en el gen MT-ND4 en heteroplasmia. La hermana del caso índice, sin manifestaciones oculares, acudió a consulta para consejo genético. El estudio de dicha mutación por secuenciación Sanger mostró que la portaba en homoplasmia. Sin embargo, mediante secuenciación de última generación (NGS) se pudo comprobar que se encontraba realmente en heteroplasmia. Conclusiones: Confirmar que una mutación se encuentra en homoplasmia es importante cara al consejo genético. Hemos observado que la NGS permite distinguir entre grados elevados de heteroplasmia y verdaderas homoplasmias y, por tanto, es de utilidad en el estudio de pacientes en los que se detectan mutaciones en homoplasmia con metodologías de menor sensibilidad analítica (AU)

Background and objective: Leber hereditary optic neuropathy is characterized by acute and subacute visual loss, produced by mitochondrial DNA mutations. Patients and methods: The molecular study of a family with only one affected member is presented. Results: In the index case and in her mother, the mitochondrial mutation m.11778G>A in the MT-ND4 was detected in the heteroplasmic state. The index case's sister, without ocular manifestations, asked for genetic counseling. The study of the mentioned mutation by Sanger sequencing identified it in an apparent homoplasmic state. However, by means of next-generation sequencing (NGS), the mutation was actually in a heteroplasmic state. Conclusions: Regarding genetic counseling, verifying a mutation in homoplasmic state is really important. We have observed that NGS allows us to discriminate between high levels of heteroplasmy and homoplasmy, meaning that it is a useful technique for the analysis of apparent homoplasmic results obtained with less sensitive technique, as Sanger sequencing (AU)

[Leber hereditary optic neuropathy: Usefulness of next generation sequencing to study mitochondrial mutations on apparent homoplasmy]. / Neuropatía óptica de Leber: utilidad de la secuenciación masiva en el estudio de mutaciones mitocondriales en aparente homoplasmia.

BACKGROUND AND OBJECTIVE: Leber hereditary optic neuropathy is characterized by acute and subacute visual loss, produced by mitochondrial DNA mutations. PATIENTS AND METHODS: The molecular study of a family with only one affected member is presented. RESULTS: In the index case and in her mother, the mitochondrial mutation m.11778G>A in the MT-ND4 was detected in the heteroplasmic state. The index case's sister, without ocular manifestations, asked for genetic counseling. The study of the mentioned mutation by Sanger sequencing identified it in an apparent homoplasmic state. However, by means of next-generation sequencing (NGS), the mutation was actually in a heteroplasmic state. CONCLUSIONS: Regarding genetic counseling, verifying a mutation in homoplasmic state is really important. We have observed that NGS allows us to discriminate between high levels of heteroplasmy and homoplasmy, meaning that it is a useful technique for the analysis of apparent homoplasmic results obtained with less sensitive technique, as Sanger sequencing.