Clinical and genetic analysis of a child with chromosomal 13q32.1-q33.3 deletion / 中华医学遗传学杂志

Objective@#To explore the genetic etiology of a child with moderate mental retardation and multiple malformations.@*Methods@#The child and his parents underwent conventional G banding karyotype analysis and single nucleotide polymorphism-based mircoarray (SNP-array) scan. A systematic review for chromosome 13q deletions was also conducted to explore the correlation between genotype and clinical phenotypes.@*Results@#G banding karyotype of the child showed a partial deletion in the long arm of chromosome 13 described as 46, XY, del(13)(q32) . SNP-array detected a deletion fragment of 11.367 Mb in 13q32.1-q33.3 region, which encompassed 30 OMIM (Online Mendelian Inheritance in Man) genes including FARP1, STK24 and ZIC2. The parents were found with no obvious abnormality in their karyotypes and SNP-array results, suggesting a de novo origin for the deletion. Combined with previous reported cases, chromosomal 13q deletions seem to have various pathogenic effects on the patients.@*Conclusion@#Chromosomal 13q32.1-q33.3 deletion probably underlies the disease phenotype in the child, and EFNB2 may be a candidate gene for congenital heart defect, genital malformation, hypospadias and anorectal malformations.

Primary Myelofibrosis with MPL S505N Mutation: The First Case Reported in Korea

MPL mutation is an important molecular marker in myeloproliferative neoplasms (MPN). Although MPL W515 is a hot spot for missense mutations in MPN, MPL S505 mutations have been reported in both familial and non-familial MPN. A 72-year-old male visited the hospital, complaining mainly of dizziness and epistaxis. Leukocytosis, anemia, thrombocytopenia, tear drop cells, nucleated RBCs, and myeloblasts were observed in both complete blood cell counts and peripheral blood smears. Bone marrow aspiration failed due to dilution with peripheral blood. BM biopsy indicated hypercellular marrow, megakaryocytic proliferation with atypia, and grade 3 reticulin fibrosis. Conventional cytogenetics results were as follows: 46,XY,del(13)(q12q22)[19]/46,XY[1]. Molecular studies did not detect JAK2 V617F, BCR/ABL translocation, JAK2 exon 12, and CALR exon 9 mutations. The MPL S505N mutation was verified by colony PCR and Sanger sequencing following gene cloning. Based on the above findings, a diagnosis of overt primary myelofibrosis (PMF) was indicated. Mutation studies of buccal and T cells were not conducted. Further, family members were not subjected to mutation studies. Therefore, we were unable to determine whether this mutation was familial or non-familial. Six months after the first visit to the hospital, the patient died due to pneumonia and sepsis. Thrombotic symptoms or major bleeding events did not develop during the survival period following diagnosis of PMF. To the best of our knowledge, this may be the first reported case of PMF with the MPL S505N mutation in Korea.

Case Report of Ring Chromosome 13: 46,xx.r(13)(p13q34)/46,xx,dicr(13;13)(p13q34;p13q34).

Aims: To report a case of ring chromosome 13 in a female child. Presentation of Case: Female, Caucasian, born in Southeast of Brazil, 6 years old. Born by cesarean section, the physical examination at 6 years and 1 month old has shown: weight of 19.100 grams and 105 centimeters tall, developmental delay, bushy eyebrows, epicanthic folds and broad nasal bridge, cardiovascular and respiratory systems were normal and no abnormalities in the limbs. Chromosome analysis was performed by GTG banding of peripheral blood and the karyotype was 46,XX,r(13)(p13q34)[97]/46,XX,dic r(13;13)(p13q34;p13q34) [3]. Analysis of 100 metaphases following G-banding revealed 97% cells with a ring chromosome 13,3% with dicentric ring chromosome of two 13s. Aneuploidy was not detected. Her parents had a normal karyotype. Discussion: Some researchers relate the clinical presentation of ring chromosome 13 with the extension of the deleted chromosomal region and instability. Others suggested that phenotypes of patients can be categorized in groups, according to the breakpoint on 13q. Conclusion: The classification of cases in groups based on breakpoints and chromosomal instability is still inaccurate, with variable phenotypes. Thus, the analysis of a greater number of cases and molecular analysis are important to establish more precise correlation between genotype and phenotype.

Phenotypical characterization of 13q deletion syndrome: Report of two cases.

Patients with 13q deletion syndrome are characterized with different phenotypical features depending on the size and location of the deleted region on chromosome 13. These patients fall into three groups: In Group 1, deleted region is in the proximal and does not extend into q32; in Group 2, deleted region involves proximal to the q32 and in Group 3 q33‑q34 is deleted. We present two cases with 13q syndrome with two different deleted region and different severity on clinical features: One case with interstitial deletion belongs to the Group 1 with mild mental retardation and minor malformations and the other case with terminal deletion belongs to Group 3 with moderate to severe mental retardation and major malformations.

A Rare Case of a de novo Proximal Deletion of 13q in a Neonate with Congenital Megacolon

Chromosome 13q deletion syndrome, which is relatively rare, is characterized by a wide spectrum of phenotypes resulting from a partial deletion of the long arm of the chromosome 13. The main clinical features are mental retardation, developmental delay, craniofacial dysmorphism, and various congenital defects. Here, we report a de novo interstitial deletion in chromosome 13 (q21.3q31) in a neonate with congenital megacolon (Hirschsprung disease) confirmed by biopsy. A short tandem repeat analysis (D13S317) was used to compare the loci on the chromosomes of the patient and the parents, the latter representing the normal karyotype, to determine how the features of the profile peaks relate to the deletion. The clinical data were also compared with those of similar cases in previously published reports.

A Case of Del 13(q24) Syndrome with Multiple Anomalies / 소아과

It has been estimated that chromosomal aberrations account for 2.3% to 3% of normal pregnancies, and of them, 85% are aborted. Therefore, the survival rate of neonates with chromosomal aberrations is very low. Among them, patients with partial deletion of the long arm of chromosome 13 are very rare. The natural history of deletion of the long arm is dependent on the deleted segment. It has been known that patients with proximal deletions not extending into q32 usually show mild to moderate mental retardation, variable minor anomalies, and growth retardation. Patients with more distal deletions, including at least part of q32, usually have severe mental retardation, growth deficiency, and major malformations including microcephaly and CNS defects, distal limb anomalies, eye defects, and gastrointestinal malformation. We report a case of a 13(q24) deletion male infant who showed intrauterine growth retardation, imperforate anus, CNS anomalies, hydronephrosis, clubfoot, clinodactyly and developmental delay, although his deletion site was proximal to q32.

A Case of Nonsyndromic Intrahepatic Bile Duct Paucity with Congenital Bilateral Vocal Cord Paralysis and 13q Deletion / 대한소아소화기영양학회지

Nonsyndromic intrahepatic bile duct paucity is known to be associated with several kinds of etiology such as infection, chromosomal anomaly, metabolic disease and idiopathic. We report a rare case of intrahepatic bile duct paucity with congenital bilateral vocal cord paralysis and 13q deletion.