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 Table of Contents  
Year : 2019  |  Volume : 3  |  Issue : 4  |  Page : 256-259

46,XY,9(p24)dup(2q35q37.3) with cryptorchidism: A case report and literature review

Department of Genetics, Northwest Women's and Children's Hospital, Xi'an 710061, China

Date of Submission07-May-2019
Date of Web Publication2-Jan-2020

Correspondence Address:
Rong Qiang
Department of Genetics, Northwest Women's and Children's Hospital, No. 1616 Yanxiang Road, Xi'an 710061
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2096-2924.274542

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A young boy with a facial abnormality was brought to our genetics clinic. Physical examination found bilateral cryptorchidism. Several clinical genetic tests, including chromosome microarray analysis (CMA), karyotyping, and azoospermia factor (AZF) microdeletions on the Y chromosome, were used to identify the genetic basis for this abnormality. The karyotype showed a duplication of the chromosome 2q35q37.3 fragment attached to chromosome 9(p24); CMA revealed 2q35q37.3(220,558,895-243,006,013)x3; the Y chromosome showed no AZF microdeletions; and the parent karyotypes were normal. Surgery has been planned to correct cryptorchidism a year after the original examination. A similar case was found previously.

Keywords: Azoospermia Factor; Chromosome Microarray Analysis; Cryptorchidism; Karyotype; Partial Trisomy of Chromosome

How to cite this article:
Wu HZ, Lou C, Liu L, Qin CY, Yan H, Qiang R. 46,XY,9(p24)dup(2q35q37.3) with cryptorchidism: A case report and literature review. Reprod Dev Med 2019;3:256-9

How to cite this URL:
Wu HZ, Lou C, Liu L, Qin CY, Yan H, Qiang R. 46,XY,9(p24)dup(2q35q37.3) with cryptorchidism: A case report and literature review. Reprod Dev Med [serial online] 2019 [cited 2020 Apr 1];3:256-9. Available from: http://www.repdevmed.org/text.asp?2019/3/4/256/274542

  Introduction Top

Cryptorchidism refers to the fact that the testicles do not descend into the scrotum within 1 year after birth; the incidence rate was around 1%. The reasons for cryptorchidism include genetics, environment, and maternal health. Cryptorchidism often occurs as a large part of congenital malformation syndromes, such as Down syndrome, Prader–Willi syndrome, and Noonan syndrome. The sex and autosome chromosome abnormalities were both related to cryptorchidism.[1],[2] Cryptorchidism can lead to infertility, cancer, and psychological consequences in the patients. We describe an unusual phenotype associated with a partial trisomy of chromosome 2 due to a translocation on chromosome 9. We were interested in the case because the described translocation is rare, the phenotype is relatively unusual, and a similar phenotype was described in another report.[3] Facial anomalies are common clinical features in chromosome diseases such as trisomy 21 syndrome, chromosome fragment deletion/duplication syndrome, or ring chromosome.[4],[5],[6],[7] The molecular genetic basis of facial anomalies is duplication or deletion of genes that lead to facial developmental abnormalities, including the SKI gene, CXADR gene, and Fibrillin-1 gene.[8],[9] We investigated the genes on this repeated chromosome 2 fragment [Table 1], attempting to find an explanation for the current clinical features and predict features in the future. Chromosome microarray analysis (CMA) is a high-resolution method to detect genotypes, referred to here as “molecular karyotyping,” which is more commonly used in clinical settings than microarray comparative genomic hybridization (array) and multiplex ligation-dependent probe amplification because of its stability and accuracy. However, next-generation sequencing represents the future for karyotyping methods. In future, it might be beneficial to design subtelomeric probes and use fluorescence in situ hybridization to confirm this specific translocation.
Table 1: Major genes expressed in the repeated block, fifteen major genes in the repeated fragment were analyzed to reveal the possible clinical features of the patient

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  Case Report Top

The patient was a 1-year-old male from the Han ethnic group. Physical features were as follows: normal hair, abnormal face, wide distance between the eyes, and small nose and nostrils [Figure 1]. His height was 100 cm; weight was 17 kg; and normal development, a steady walk, and a normal knee reflex were observed. No clearance of the palm was observed, and a short knuckle on the hand was found [Figure 2]. Bilateral cryptorchidism, an empty scrotum, and normal penile development were observed (privacy). The patient was a term 1 child, with a pregnancy age of 40 weeks, birth weight of 3.5 kg, no skin jaundice, meconium aspiration pneumonia, mild asphyxia, a rescue history after birth, neonatal intensive care unit observation for 2 h, mild ischemic encephalopathy, scalp hematoma, and a congenital heart disease-ventricular septal defect that was self-healed 6 months later. No consanguineous marriage and no similar patients in either family were found, and other examinations were normal. Biochemistry parameters were as follows: (1) 17-αOH progesterone: 3.66 nmol/L, (2) phenylalanine: 1.40 mg/dL, (3) thyroid-stimulating hormone: 0.67 mU/L, and (4) glucose-6-phosphate dehydrogenase: 4.82 U/gHb.
Figure 1: Patient's face with wide binocular distance, low-level nasal bridge, and diagonal canthi.

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Figure 2: Patient's right hand with short dactylopodites on the little finger.

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Cytogenetic examination: The child underwent peripheral blood lymphocyte culture, production, and G banding. By counting 20 metaphase cells, 3 division karyotypes were analyzed [Figure 3]. Parents' karyotypes are normal. CMA showed 2q35q37.3 (220,558,895-243,006,013)x3 [Figure 4].
Figure 3: Patient's karyotype. The chromosome 9 on the right side is longer than that on the left side, G-banding software found an extra band on the longer chromosome 9.

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Figure 4: Chromosome microarray analysis result. A duplication fragment from chromosome 2 (the pink fragment) was found by CMA: arr[hg19] 2q35q37.3(220,558,895-243,006,013)x3.

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The chromosome 9 on the right side is bigger than chromosome 9 on the left side, G-banding software was used to analyze the bands on the two chromosome 9, and the results showed that the karyotype of the patient was 46, XY,9(p24)dup(2q35q37.3).

The chromosome copy number variation was found by CMA in the patient; it was a duplication fragment from chromosome 2 (the pink fragment): arr[hg19] 2q35q37.3 (220,558,895-243,006,013)x3.

Y chromosome microdeletion was done for the child; polymerase chain reaction was used to amplify the sequence-tagged sites on Y chromosome. This experiment was performed in accordance with the European Association of Urology and the European Molecular Genetic Quality Network 2013 edition standard for testing. No deletions were found in azoospermia factor (AZF) area on Y chromosome [Table 2].
Table 2: Y chromosome microdeletions

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  Discussion Top

Chromosome duplication of one segment is a common change, which is strongly related to a change in gene function due to repeated gene fragments. This patient had an approximately 22.45 Mb 2q35-q37.3 region on chromosome 2 repeated on chromosome 9p24. A section with a lack of variation (associated with “2q37 Microdeletion syndrome”[10] and “Waardenburg syndrome type 1”[11]) can often cause mental retardation, skeletal deformity, nasal dysplasia, absent/small/flat noses, micrognathia, hypertelorism, and other abnormal appearance symptoms. Other patients also show sensorineural hearing loss; lateral displacement; multiple congenital cardiovascular disease; and inner canthus, skin, hair, and iris pigment abnormalities; however, the correlation between repeats and disease in this variant section has not been reported. In addition, the translocation effect is unknown. The patient of this study has a facial abnormality, and his IQ could not be detected; it is not known whether he has intelligence problems or other mental abnormalities, and therefore, there is still a need for further observation. Our recommendations are as follows: (1) conduct a comprehensive evaluation of the growth and development of children in the pediatric specialist clinic and (2) record and follow up the child's growth process.

Upon querying the NCBI database, we found that this duplication fragment contains hundreds of genes [selection of 15 major genes, [Table 1], such as BOK, insulin receptor substrate 1 (IRS1), and programmed cell death 1 (PDCD1), which have been found to play an important role in human development. Bcl-2-related ovarian killer (BOK) is a proapoptotic member of the Bcl-2 family (B-cell lymphoma/leukemia-2),[12] which contains key regulatory factors to determine the survival or apoptosis of eukaryotic cells. Researchers found expression of BOK in zebrafish ovaries, testes, eyes, and livers; others have found BOK expression to be highest in human testes, with ovaries having similarly high expression. These findings indicate that abnormal expression of BOK may cause cryptorchidism; this hypothesis needs to be studied further. IRS1[13] is mainly related to atherosclerosis in diabetes, which will lead to abnormal blood pressure, an increase in blood plasma triglycerides, and a decrease in lipoprotein lipase activity, all of which increase coronary artery disease risk. However, these results were found in mice, and the impact on humans has not been studied in depth. PDCD1[14] is a protein associated with gene expression in the thymus. When an anti-CD3 antibody was injected into the thymus, PDCD1 was upregulated and led to significant thymocyte apoptosis, resulting in abnormal cardiovascular dilation and congestive heart failure.[15]

Some of the patient's characteristics match the deletion of the chromosome fragment, such as nasal dysplasia, small nose, and hypertelorism, which shows that a lack of gene expression and gene overexpression can sometimes have identical results. Patients with congenital heart disease always have chromosomal abnormalities, and chromosome-related disease is accompanied by many developmental problems in the heart, which holds true in this case. However, in this case, the heart self-healed at 6 months of age. There is no consistent relationship between cryptorchidism and chromosomal abnormalities: there are reports of patients with ring chromosome 4 having cryptorchidism;[16] DAZ gene deletion on the Y chromosome and cryptorchidism are not directly related;[17],[18] and some studies have claimed that AZFc deficiency is one of the causes of cryptorchidism,[19],[20],[21] but in these cases, Y chromosome microdeletion detection resulted in no loss of AZFc, and thus, this purported causal link still deserves scrutiny. Chromosomal abnormalities are associated with cryptorchidism, but this case still needs to be studied. We have successfully finished surgery and discharged the patient in good condition, and the patient was able to walk normally.

Chromosomes carry genetic information, gene number does not change, and gene locations are fixed on the chromosome; otherwise, there are a number of problems. The chromosomes will pair, divide, and combine after fertilization, create a new organism, and in this process, mismatched combinations will result in chromosome breakage, duplication, and loss. The offspring will have atypical numbers and positions of genes on the chromosome and will appear abnormal, but why do these mistakes occur? Environmental factors are important in determining chromosomal structure and number: bacterial infection, physical and chemical factors, unbalanced nutritional intake, suboptimal lifestyle choices, psychological pressure, etc., can ultimately cause chromosomal problems in children.

The parents of the child in question are still young (both 26 years old), with normal chromosomes. Their ova and sperm show no signs of aging, and they want to have another child. They should therefore keep these problems in mind during their next pregnancy. They should undergo the necessary checks at the Department of Gynecology and Andrology, improve ovarian function, improve nutrition, and avoid adverse environmental factors to create the best chance of giving birth to a healthy baby.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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Dutta MK, Gundgurthi A, Garg MK, Pakhetr R. Cryptorchidism due to chromosome 5q inversion duplication. J Assoc Physicians India 2013;61:925-7.  Back to cited text no. 2
Hermsen MA, Tijssen M, Acero IH, Meijer GA, Ylstra B, Toral JF. High resolution microarray CGH and MLPA analysis for improved genotype/phenotype evaluation of two childhood genetic disorder cases: Ring chromosome 19 and partial duplication 2q. Eur J Med Genet 2005;48:310-8. doi: 10.1016/j.ejmg.2005.04.009.  Back to cited text no. 3
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Wallberg M, Recino A, Phillips J, Howie D, Vienne M, Paluch C. Anti-CD3 treatment up-regulates programmed cell death protein-1 expression on activated effector T cells and severely impairs their inflammatory capacity. Immunology 2017;151:248-60. doi: 10.1111/imm.12729.  Back to cited text no. 15
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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2]


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