Prenatal Diagnosis of Combined Maternal 4q Interstitial Deletion and Paternal 15q Microduplication

The 4q deletion syndrome is a well-known rare genetic condition caused by partial, terminal, or interstitial deletion in the long arm (q) of chromosome 4. The phenotype of this syndrome shows a broad spectrum of clinical manifestations due to the great variability in the size and location of the deletion. In the literature, the mostly terminal deletions of chromosome 4q and the relative phenotypes are described, while the interstitial deletions of the long arm of chromosome 4 are rarely cited. Here, we report on a female fetus presenting no abnormal ultrasound evidence but with multiple chromosome aberrations. Comparative genomic hybridization (aCGH) revealed an interstitial 10.09 Mb deletion at the chromosome at the region of 4q28, arr[hg19] 4q28.1q28.3 (124068262_134158728)x1 combined with a 386.81 Kb microduplication at chromosome 15q11.1, arr[hg19] 15.11 (20249932_20636742)x3. At birth, and after 11 months, the baby was confirmed healthy and normal. The identification of this case allows for a deeper understanding of 4q syndrome and provides an explanation for the wide genetic/phenotypic spectrum of this pathology. This report can provide a reference for prenatal diagnosis and genetic counseling in patients who have similar cytogenetic abnormalities, and underlines the importance of reporting unusual variant chromosomes for diagnostic genetic purposes.

Potential Prognostic Significance of Patterns of Deletion (13q) in Plasma Cell Myelomas—Reappraisal of a Perennial Bone of Contention

Deletion 13q is recommended in the initial cytogenetic workup of myeloma patients. The patterns of this abnormality have been shown to have differential prognostic value. The presence of monosomy 13 is associated with a significantly poor progression-free survival, while interstitial deletion 13q is associated with significant improvement in the overall survival. We analyzed the patterns of 13q abnormalities on fluorescent in situ hybridization (FISH) assay results in myeloma patients. Deletion 13q abnormalities were observed in 38% (55 of 138) of the myeloma patients. Ten (18%) and 44 (80%) patients showed interstitial deletion and terminal deletion, respectively. One had a mosaic of both the patterns. Nine of the ten patients with interstitial deletions were males. For terminal deletion 13q, there appeared to be a slight female predilection, with a male to female ratio of 0.83:1. Half of the patients with deletion 13q had coexistent cytogenetic abnormalities. We suggest a baseline FISH for deletion 13q and specification of the type of abnormality (terminal vs. interstitial) in patients with myeloma. Based on our observation in conjunction with the available literature, further studies in a large cohort of patients with survival data are warranted to clearly delineate the role of deletion 13q in myeloma.

Case of interstitial deletion of the short arm of chromosome 9 associated with disorders of sex development

Делеции короткого плеча хромосомы 9 представляют собой клинически и генетически гетерогенную группу. Большинство описанных случаев представляют собой терминальные делеции или несбалансированные транслокации с различными с точками разрыва на коротком плече хромосомы 9. Интерстициальные делеции короткого плеча хромосомы 9 - крайне редко встречающаяся хромосомная патология. Мы сообщаем о пациенте с задержкой психомоторного развития, гипоплазией мозжечка и гипоспадией у которого при проведении хромосомного микроматричного анализа диагностирована интерстициальная делеция 9p24.3-p23, затрагивающая ген DMRT1. Deletions of the short arm of chromosome 9 are a clinically and genetically heterogeneous group. Most of the cases described are terminal deletions or unbalanced translocations with different break points on the short arm of chromosome 9. Interstitial deletions of the short arm of chromosome 9 are an extremely rare chromosome pathology. We report a patient with developmental and psychomotor delay, cerebellar hypoplasia and hypospadias, who was diagnosed with interstitial 9p24.3-p23 deletion affecting the DMRT1 gene during chromosome microarray analysis (СMA).

Studies of mice deleted for Sox3 and uc482: relevance to X-linked hypoparathyroidism

Hypoparathyroidism is genetically heterogeneous and characterized by low plasma calcium and parathyroid hormone (PTH) concentrations. X-linked hypoparathyroidism (XLHPT) in two American families is associated with interstitial deletion-insertions involving deletions of chromosome Xq27.1 downstream of SOX3 and insertions of predominantly non-coding DNA from chromosome 2p25.3. These could result in loss, gain, or movement of regulatory elements, which include ultraconserved element uc482, which could alter SOX3 expression. To investigate this, we analysed SOX3 expression in EBV-transformed lymphoblastoid cells from three affected males, three unaffected males, and four carrier females from one XLHPT family. SOX3 expression was similar in all individuals, indicating that the spatiotemporal effect of the interstitial deletion-insertion on SOX3 expression postulated to occur in developing parathyroids did not manifest in lymphoblastoids. Expression of SNTG2, which is duplicated and inserted into the X chromosome, and ATP11C, which is moved telomerically, were also similarly expressed in all individuals. Investigation of male hemizygous (Sox3−/Y and uc482−/Y) and female heterozygous (Sox3+/− and uc482+/−) knockout mice, together with wild-type littermates (male Sox3+/Y and uc482+/Y, and female Sox3+/+ and uc482+/+), revealed Sox3−/Y, Sox3+/−, uc482−/Y, and uc482+/− mice to have normal plasma biochemistry, compared to their respective wild-type littermates. When challenged with a low calcium diet, all mice had hypocalcaemia, and elevated plasma PTH concentrations and alkaline phosphatase activities, and Sox3−/Y, Sox3+/−, uc482−/Y, and uc482+/− mice had similar plasma biochemistry, compared to wild-type littermates. Thus, these results indicate that absence of Sox3 or uc482 does not cause hypoparathyroidism and that XLHPT likely reflects a more complex mechanism.