Genetic analysis of a fetus with mosaicism of 13q inversion duplication / 中华医学遗传学杂志

OBJECTIVE@#To report on a case of mosaicism 13q inversion duplication, analyze its mechanism, and discuss the correlation between its genotype and phenotype.@*METHODS@#Amniotic fluid and umbilical cord blood were collected at 23 and 32 weeks of gestation, respectively. Combined with G-banding chromosome karyotyping analysis, single nucleotide polymorphism array (SNP-array) and fluorescence in situ hybridization (FISH) were used to confirm the result.@*RESULTS@#The karyotype of the fetus was determined as 47,XY,+inv dup(13)(q14.3q34)/46,XY. After careful counseling, the couple decided to continue with the pregnancy, and had given birth to a boy at 40 weeks' gestation. Except for a red plaque (hemangioma) on the nose bridge, no obvious abnormality (intelligence to be evaluated) was discovered.@*CONCLUSION@#To provide reference for clinical genetic counseling and risk assessment, the location and proportion of new centromere formation should be fully considered in the case of mosaicism 13q inversion duplication.

Analysis of gene inversion in Hemophilia A by Nanopore sequencing / 中华医学遗传学杂志

OBJECTIVE@#To detect gene inversion in two pedigrees affected with Hemophilia A by using Nanopore sequencing technology.@*METHODS@#Peripheral blood samples were taken from members of the two pedigrees. Following extraction of genome DNA, genetic variants of the carriers were detected by Nanopore sequencing and subjected to bioinformatic analysis.@*RESULTS@#Nanopore sequencing has identified the niece of the proband of the pedigree 1 as carrier of Hemophilia A Inv22, and the mother of the proband of the pedigree 2 as carrier of Hemophilia A Inv1, which was consistent with clinical findings. Breakpoint sites in both pedigrees were accurately mapped. Statistical analysis of the sequencing results revealed a large number of variations in the carriers' genomes including deletions, duplications, insertions, inversions and translocations.@*CONCLUSION@#Nanopore sequencing can be used to analyze gene inversions associated with Hemophilia A, which also provided a powerful tool for the diagnosis of diseases caused by gene inversions.

Anopheles darlingi polytene chromosomes: revised maps including newly described inversions and evidence for population structure in Manaus

Salivary gland polytene chromosomes of 4th instar Anopheles darlingi Root were examined from multiple locations in the Brazilian Amazon. Minor modifications were made to existing polytene photomaps. These included changes to the breakpoint positions of several previously described paracentric inversions and descriptions of four new paracentric inversions, two on the right arm of chromosome 3 and two on the left arm of chromosome 3 that were found in multiple locations. A total of 18 inversions on the X (n = 1) chromosome, chromosome 2 (n = 7) and 3 (n = 11) were scored for 83 individuals from Manaus, Macapá and Porto Velho municipalities. The frequency of 2Ra inversion karyotypes in Manaus shows significant deficiency of heterozygotes (p < 0.0009). No significant linkage disequilibrium was found between inversions on chromosome 2 and 3. We hypothesize that at least two sympatric subpopulations exist within the An. darlingi population at Manaus based on inversion frequencies.

The First Korean Case of Childhood Acute Myeloid Leukemia with Inv(11)(p15q22)/NUP98-DDX10 Rearrangement: A Rare but Recurrent Genetic Abnormality

No abstract available.

A familial deletion 4q syndrome: An outcome of a paracentric inversion.

Chromosome inversions are intra-chromosomal rearrangements formed when the chromosome breaks occur at two places, and in the process of repair the intervening segments are joined in an inverted or opposite manner. Inversions themselves do not appear to cause clinical anomalies, if balanced. Abnormal phenotypes can occur due to gene disruption at the point of breakage and reunion or due to duplication/deficiency recombinants formed during crossover at meiosis. We report a case with familial deletion 4q syndrome in a 1-year-old female child with dysmorphism and congenital abnormalities. The deletion was an outcome of a paracentric inversion 4q31.2q35.2. The deletion was confirmed by fluorescence in situ hybridization using telomeric DNA probes for chromosome No. 4. An attempt was made to correlate the genotype with the phenotype. The father had the same rearrangement with a milder phenotype. The recurrence risk in such cases is high.

De Novo Pericentric Inversion of Chromosome 9 in Congenital Anomaly

PURPOSE: The pericentric inversion of chromosome 9 is one of the most common structural balanced chromosomal variations and has been found in both normal populations and patients with various abnormal phenotypes and diseases. The aim of this study was to re-evaluate the clinical impact of inv(9)(p11q13). MATERIALS AND METHODS: We studied the karyotypes of 431 neonates with congenital anomalies at the Pediatric Clinic in Ajou University Hospital between 2004 and 2008 and retrospectively reviewed their clinical data. RESULTS: Chromosomal aberrations were detected in 60 patients (13.9%). The most common type of structural abnormality was inv(9)(p11q13), found in eight patients. Clinical investigation revealed that all eight cases with inv(9)(p11q13) had various congenital anomalies including: polydactyly, club foot, microtia, deafness, asymmetric face, giant Meckel's diverticulum, duodenal diaphragm, small bowel malrotation, pulmonary stenosis, cardiomyopathy, arrhythmia, and intrauterine growth restriction. The cytogenetic analysis of parents showed that all of the cases were de novo heterozygous inv(9)(p11q13). CONCLUSION: Since our results indicate that the incidence of inv(9)(p11q13) in patients with congenital anomalies was not significantly different from the normal population, inv(9)(p11q13) does not appear to be pathogenic with regard to the congenital anomalies. Some other, to date unknown, causes of the anomalies remain to be identified.

A Case of Weill-Marchesani Syndrome with Inversion of Chromosome 15

PURPOSE: To present a case of Weill-Marchesani syndrome with corneal endothelial dysfunction due to anterior dislocation of a spherophakic lens and corneolenticular contact. METHODS: A 17-year-old woman presented with high myopia and progressive visual disturbance. She was of short stature and had brachydactyly. Her initial Snellen best corrected visual acuity (BCVA) was 20/50 (-sph 20.50 -cyl 3.00 Ax 180) in her right eye and 20/40 (-sph 16.00 -cyl 6.00 Ax 30) in her left eye. Slit lamp examination revealed a dislocated spherophakic lens touching corenal endothelium. A microspherophakic lens, hypoplastic ciliary body, and elongated zonules were confirmed on rotating Scheimpflug camera (Pentacam(R)) and on ultrasound biomicroscopy. Specular microscopy showed corneal endothealial dysfunction. Systemic evaluation was performed, and chromosomal study showed 46, XX, inv (15) (q13qter). The patient was diagnosed with Weill-Marchesani syndrome. RESULTS: Due to impending corneal decompensation, phacoemulsification and suture fixation of the intraocular lens were performed. The operation and postoperative course were uneventful. Three months postoperatively, the visual acuity was 20/30 (OD) and 20/40 (OS) without correction, and BCVA was 20/20 (+sph 0.50 -cyl 2.00 Ax 160 : OD) and 20/25 (+sph 1.50 -cyl 3.00 Ax 30 : OS). During the follow-up period, increased corneal endothelial counts, hexagonality, and decreased corneal thickness were achieved. CONCLUSIONS: In Weill-Marchesani syndrome with a chromosomal anomaly, a dislocated spherophakic lens may cause severe corneal endothelial dysfunction due to corneolenticular contact, and prompt lensectomy is important to prevent such complications.

Genética de la hemofilia humana. Diagnóstico molecular de defectos en los genes de los factores VIII y IX de coagulación / Genetics of human haemophilia. Molecular diagnosis of defects affecting coagulation factors VIII and IX

La hemofilia A (HA) y B (HB) son enfermedades hemorrágicas hereditarias ligadas al sexo causadas por defectos de los factores VIII y IX, respectivamente. Excepto grandes inversiones recurrentes involucradas en la mitad de las HA severas, el resto de las hemofilias son causadas por distintos tipos de mutaciones grandes y pequeñas. Fueron estudiadas 70 familias con HA severa (se), 6 con seHB, 1 con HA moderada-leve (m) y 2 con mHB. Primero, en seHA, se estudio la inversión del intrón 22 (Inv22) usando un nuevo abordaje basado en PCR inversa. En los casos negativos para las inversiones se estudiaron primariamente las grandes deleciones y secundariamente las mutaciones pequeñas. En familias con HA, encontramos la Inv22 en 43 por ciento de las seHAs, una única inversión del intrón 1, 10 grandes deleciones (catorce por ciento)y 23 mutaciones pequeñas (incluyendo 10 deleciones, 3 inserciones, 4 cambios nonsense, 5 missense y 1 de splicing); y en HB, 1 deleción afectando un sitio de splicing, 4 missense y 3 nonsense. Este esquema de caracterización de mutaciones permite un estudio y análisis molecular preciso de HA y HB y beneficiará tanto al asesoramiento genético como a la provisión de información clave para el diseño del tratamiento.

Familial pericentric inversion of chromosome 1, inv [1] [p11: q21] associated with inguinal hernia in Bedoum sibs

Inguinal hernia and pericentric inversion of chromosome 1 are described in 2 bedouin sibs. The coexistence support the hypothesis of genetic predisposition