Arvind Babu

Mosaicism for a small supernumerary ring X chromosome in a dysmorphic, growth-retarded male: mos47,XXY/48,XXY, + r(X)

Supernumerary ring X [r(X)] chromosomes are often found in patients with Turner syndrome. The phenotypic effects of the r(X) chromosome are variable, and largely depend on the presence or absence of the X inactivation (XIST) locus. Ring(X) chromosomes in males are rare and have been previously reported in only four cases, with 47,XY, + r(X) or mos47,XY, + r(X)/46,XY karyotypes. These patients all had developmental delay and dysmorphic features. We describe a 2.5‐year‐old male patient with facial dysmorphia, growth retardation, microcephaly, global developmental delay, and microphallus. Cytogenetic analysis from peripheral blood lymphocytes and fibroblasts identified mosaicism for two cell lines: mos48,XXY, + r(?X)/47,XXY. Fluorescence in situ hybridization (FISH) with an X chromosome paint showed the ring chromosome to be X chromosome derived. This is the first case of an r(X) chromosome described in a 47,XXY patient. FISH analysis of the r(X) chromosome with an XIST probe showed that the XIST locus was absent. Functional disomy of genes in the r(X) chromosome most likely accounts for the abnormal phenotype in the proband.

Prenatal detection and molecular characterization of a de novo duplication of the distal long arm of chromosome 19

A tandem duplication of the distal long arm of chromosome 19 was identified in a 10 week fetus by analysis of chorionic villi. The fetal karyotype from two primary cultures was 46,XY,dir dup(19)(q13.2q13.4). The origin of the extra material was confirmed by fluorescence in situ hybridization using a chromosome 19 whole chromosome probe. Parental chromosomes were normal, indicating a de novo origin of the extra chromosome material. This is the first case of dup(19q) detected by prenatal diagnosis. Molecular studies demonstrated that the duplication involved a maternal chromosome 19.

T‐cell chronic lymphocytic leukemia. Unusual morphologic, phenotypic, and karyotypic features in association with light chain amyloidosis

Background. Lymphocytes that display a phenotype of mature B‐cells, T‐cells, natural killer (NK) cells, or a combination of T‐cells and NK cells can be found in patients with lymphoproliferations that manifest as expansions of peripheral blood lymphocytes (PBL). If these PBL expansions exhibit clonality, they can be classified as chronic lymphocytic leukemia (CLL).

Prenatal diagnosis of a familial interchromosomal insertion of Y chromosome heterochromatin

An apparently unbalanced karyotype containing an abnormal chromosome 11 was identified in a 16-week female fetus by analysis of cultured amniocytes. Fluorescence in situ hybridization (FISH) with a chromosome 11 paint identified the presence of an insertion in band 11q24. Parental karyotyping documented an unbalanced karyotype with the same der(11) chromosome in the phenotypically normal father. CBG-banding and FISH identified the insertion to be Yq12 heterochromatin: 46,XY, der(11)ins(11;Y)(q24;q12q12).ish der(11) (wcp11+,DYZ1+). The same der(11) chromosome was also found in the phenotypically normal paternal grandmother, demonstrating this additional Y chromosomal material did not affect normal female sexual development or fertility. The parents elected to continue the pregnancy and a normal girl was born at term, further confirming that this rare familial variant has no clinical significance. This case illustrates the importance of family studies, appropriate banding, and FISH analyses to accurately characterize apparent chromosomal abnormalities.

Application of DA/DAPI Technique in Cancer Cytogenetics

The recent advent of banding techniques has facilitated the identification of human chromosomal abnormalities in neoplasias. Utilization of a single technique for the identification of marker chromosomes has caused ambiguity because staining profiles overlap with many other chromosomal regions in the human genome. Thus, the implication of DA/DAPI technique in clinical cytogenetics has been documented by presenting a variety of cases with neoplastic syndromes.

The Soliga, an isolated tribe from Southern India: genetic diversity and phylogenetic affinities

Indias role in the dispersal of modern humans can be explored by investigating its oldest inhabitants: the tribal people. The Soliga people of the Biligiri Rangana Hills, a tribal community in Southern India, could be among the countrys first settlers. This forest-bound, Dravidian speaking group, lives isolated, practicing subsistence-level agriculture under primitive conditions. The aim of this study is to examine the phylogenetic relationships of the Soligas in relation to 29 worldwide, geographically targeted, reference populations. For this purpose, we employed a battery of 15 hypervariable autosomal short tandem repeat loci as markers. The Soliga tribe was found to be remarkably different from other Indian populations including other southern Dravidian-speaking tribes. In contrast, the Soliga people exhibited genetic affinity to two Australian aboriginal populations. This genetic similarity could be attributed to the ‘Out of Africa’ migratory wave(s) along the southern coast of India that eventually reached Australia. Alternatively, the observed genetic affinity may be explained by more recent migrations from the Indian subcontinent into Australia.

Congenital adrenal hyperplasia in monozygotic twins with variable clinical manifestations.

SummaryThe first cases of congenital adrenal hyperplasia III with variable clinical manifestations in female monozygotic twins are presented. Twin “A” revealed severe hypertrophy of the clitoris, labial fusion and a visible introitus. However, twin “B” manifested moderate clitoral hypertrophy, a visible introitus and no labial fusion. Neither infant had palpable gonads.

Prenatal diagnosis and outcome of mosaicism for a de novo unbalanced translocation identified in amniocytes

Mosaicism for an unbalanced reciprocal translocation was identified in cultured amniocytes of a 16‐week‐old fetus; mos46,XX,der(4)t(4;5)(q34;q12)/46,XX. Parental karyotypes were normal, indicating a de novo origin of the unbalanced translocation in the fetus. The additional chromosomal material on the der(4) was derived from chromosome 5 as demonstrated by both GTG banding and fluorescence in situ hybridization with a chromosome 5 paint. Two subsequent amniocenteses, at 18 and 20 weeks, confirmed the presence of the abnormal cell line. A percutaneous umbilical blood sample (PUBS) contained only normal cells, 46,XX, and a high resolution ultrasound revealed no fetal abnormalities or growth retardation. The pregnancy was continued and a normal female was born at term. No evidence of the unbalanced translocation cell line was found in cord blood or placental samples at birth. The finding of mosaicism for an unbalanced translocation at amniocentesis is rare, and is associated with a high risk of fetal abnormality. This case illustrates the importance of follow‐up studies by PUBS and high‐resolution ultrasound for further assessing the risk of phenotypic abnormality.

Maternal uniparental disomy of chromosome 15 and concomitant STRC and CATSPER2 deletion-mediated deafness-infertility syndrome

1Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 2Division of Neonatology, Mount Sinai West, New York, New York Correspondence Stuart A. Scott, Ph.D., Assistant Professor. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1497, New York 10029, NY. Email: stuart.scott@mssm.edu Funding information National Institute of General Medical Sciences (NIGMS), Grant number: K23 GM104401 K E YWORD S CATSPER2, chromosome 15, deafness-infertility syndrome, Prader–Willi syndrome, STRC, uniparental disomy