A Novel Pathogenic Variant in the MN1 Gene in a Patient Presenting with Rhombencephalosynapsis and Craniofacial Anomalies, Expanding MN1 C-terminal Truncation Syndrome.

Meningioma-1 is a transcription activator that regulates mammalian palate development and is required for appropriate osteoblast proliferation, motility, differentiation, and function. Microdeletions involving the MN1 gene have been linked to syndromes including craniofacial anomalies, such as Toriello-Carey syndrome. Recently, truncating variants in the C-terminal portion of the MN1 transcriptional factor have been linked to a characteristic and distinct phenotype presenting with craniofacial anomalies and partial rhombencephalosynapsis, a rare brain malformation characterized by midline fusion of the cerebellar hemispheres with partial or complete loss of the cerebellar vermis. It has been called MN1 C-terminal truncation (MCTT) syndrome or CEBALID (Craniofacial defects, dysmorphic Ears, Brain Abnormalities, Language delay, and Intellectual Disability) and suggested to be caused by dominantly acting truncated protein MN1 instead of haploinsufficiency. As a proto-oncogene, MN1 is also involved in familial meningioma. In this study, we present a novel case of MCTT syndrome in a female patient presenting with craniofacial anomalies and rhombencephalosynapsis, harboring a de novo pathogenic variant in the MN1 gene: c.3686_3698del, p.(Met1229Argfs*87).

[Electroclinical characteristics of a patient with ring chromosome 20 syndrome]. / Características electroclínicas de un paciente con síndrome del cromosoma 20 en anillo.

INTRODUCTION: The ring chromosome 20 syndrome (r20) is a rare genetic disorder with a late diagnosis. CASE REPORT: A 17 year old boy with drug-resistant epilepsy of 14 years of evolution, which has moderate mental retardation, behavioral alterations and seizures consisting of complex non-convulsive status and generalized seizures during wakefulness, along with more subtle epileptic manifestations during sleep. Karyotype in peripheral blood showed the existence of a ring chromosome 20, whose breakpoints were p13q13.3, presenting a mosaicism 46,XY[23]/46,XY,r(20)(p13q13.3)[25]. CONCLUSIONS: The epileptic r20 syndrome seems to have a characteristic electroclinical phenotype and, although not pathognomonic, should be sufficient for all patients who meet a karyotype in peripheral blood, thus avoiding multiple trials with unnecessary drugs and exhaustive studies. In this sense, the study of sleep EEG may be helpful.

TITLE: Caracteristicas electroclinicas de un paciente con sindrome del cromosoma 20 en anillo.Introduccion. El sindrome del cromosoma 20 en anillo (r20) es una alteracion genetica infrecuente, con un diagnostico tardio. Caso clinico. Varon de 17 años con epilepsia farmacorresistente de 14 años de evolucion, que presentaba retraso mental moderado, alteraciones conductuales y crisis epilepticas consistentes en estados complejos no convulsivos y crisis generalizadas durante la vigilia, junto con manifestaciones epilepticas mas sutiles durante el sueño. El estudio del cariotipo en sangre periferica mostro la existencia de un cromosoma 20 en anillo, cuyos puntos de corte parecen ser p13q13.3, y presento un mosaicismo 46,XY[23]/46,XY,r(20)(p13q13.3)[25]. Conclusiones. El sindrome epileptico r20 parece tener un fenotipo electroclinico caracteristico y, aunque no es patognomonico, deberia ser suficiente para realizar en todos los pacientes que lo cumplan un cariotipo en sangre periferica, que evite asi los multiples ensayos con farmacos y estudios exhaustivos innecesarios. En ese sentido, el estudio electroencefalografico de sueño puede resultar de gran ayuda.

Características electroclínicas de un paciente con síndrome del cromosoma 20 en anillo / Electroclinical characteristics of a patient with ring chromosome 20 syndrome

Introducción. El síndrome del cromosoma 20 en anillo (r20) es una alteración genética infrecuente, con un diagnóstico tardío. Caso clínico. Varón de 17 años con epilepsia farmacorresistente de 14 años de evolución, que presentaba retraso mental moderado, alteraciones conductuales y crisis epilépticas consistentes en estados complejos no convulsivos y crisis generalizadas durante la vigilia, junto con manifestaciones epilépticas más sutiles durante el sueño. El estudio del cariotipo en sangre periférica mostró la existencia de un cromosoma 20 en anillo, cuyos puntos de corte parecen ser p13q13.3, y presentó un mosaicismo 46,XY[23]/46,XY,r(20)(p13q13.3)[25]. Conclusiones. El síndrome epiléptico r20 parece tener un fenotipo electroclínico característico y, aunque no es patognomónico, debería ser suficiente para realizar en todos los pacientes que lo cumplan un cariotipo en sangre periférica, que evite así los múltiples ensayos con fármacos y estudios exhaustivos innecesarios. En ese sentido, el estudio electroencefalográfico de sueño puede resultar de gran ayuda (AU)

Introduction. The ring chromosome 20 syndrome (r20) is a rare genetic disorder with a late diagnosis. Case report. A 17 year old boy with drug-resistant epilepsy of 14 years of evolution, which has moderate mental retardation, behavioral alterations and seizures consisting of complex non-convulsive status and generalized seizures during wakefulness, along with more subtle epileptic manifestations during sleep. Karyotype in peripheral blood showed the existence of a ring chromosome 20, whose breakpoints were p13q13.3, presenting a mosaicism 46,XY[23]/46,XY,r(20)(p13q13.3)[25]. Conclusions. The epileptic r20 syndrome seems to have a characteristic electroclinical phenotype and, although not pathognomonic, should be sufficient for all patients who meet a karyotype in peripheral blood, thus avoiding multiple trials with unnecessary drugs and exhaustive studies. In this sense, the study of sleep EEG may be helpful (AU)

Analysis of follicular fluid and serum markers of oxidative stress in women with infertility related to endometriosis.

OBJECTIVE: To study the levels of four markers of oxidative stress in follicular fluid (FF) and plasma of patients with infertility related to endometriosis and controls. DESIGN: Experimental study. SETTING: University-affiliated hospital and infertility center. PATIENT(S): Ninety-one infertile women were included in the study (23 infertile women with endometriosis and 68 controls including infertile women due to tubal factor, male factor, or healthy egg donors). INTERVENTION(S): Blood was obtained at the time of egg retrieval, and FF from the mature follicles of each ovary was centrifuged and frozen until analysis. MAIN OUTCOME MEASURE(S): Vitamin C and E, malondialdehyde, and superoxide dismutase concentrations in plasma and follicular fluid. RESULT(S): Women with endometriosis showed a lower vitamin C concentration in FF (12.7 ± 5.9 vs. 9.7 ± 6.9 µg/mL) and lower superoxide dismutase concentration in plasma (0.9 ± 1.4 vs. 0.5 ± 0.7 U/mL) compared with controls. Vitamin E plasma levels were significantly higher in women with endometriosis (8.1 ± 3.8 vs. 5.2 ± 3.2 µg/mL). A nonsignificant trend toward a lower plasma concentration of malondialdehyde was found in women with endometriosis. CONCLUSION(S): These findings suggest a lower antioxidant capacity in infertile women with endometriosis. Although a certain level of reactive oxygen species is required under physiological conditions, an altered balance between pro-oxidant and antioxidant activities may have an impact on folliculogenesis and adequate embryo development.

Screening for mutations in Spanish families with myotonia. Functional analysis of novel mutations in CLCN1 gene.

Myotonia congenita is an inherited muscle disorder caused by mutations in the CLCN1 gene, a voltage-gated chloride channel of skeletal muscle. We have studied 48 families with myotonia, 32 out of them carrying mutations in CLCN1 gene and eight carry mutations in SCN4A gene. We have found 26 different mutations in CLCN1 gene, including 13 not reported previously. Among those 26 mutations, c.180+3A>T in intron 1 is present in nearly one half of the Spanish families in this series, the largest one analyzed in Spain so far. Although scarce data have been published on the frequency of mutation c.180+3A>T in other populations, our data suggest that this mutation is more frequent in Spain than in other European populations. In addition, expression in HEK293 cells of the new missense mutants Tyr137Asp, Gly230Val, Gly233Val, Tyr302His, Gly416Glu, Arg421Cys, Asn567Lys and Gln788Pro, demonstrated that these DNA variants are disease-causing mutations that abrogate chloride currents.