Abstract
Introduction: Isodicentric Y chromosomes are relatively common structural variants of the human genome. The underlying mechanism of isodicentric Y chromosomes with short arm breakpoints [idic(Yq)] remains to be clarified. Case Presentation: We encountered a Japanese man with azoospermia and mild short stature. G-banding and array-based comparative genomic hybridization indicated that his karyotype was 45,X/46,X,idic(Y)(qter→p11.32::p11.32→qter) with a ∼1.8 Mb terminal deletion. Whole-genome sequencing suggested that the Y chromosome had four breakpoints in a ∼7 kb region of the pseudoautosomal region 1 (PAR1). Conclusion: This case was assumed to have an idic(Yq) resulting from multiple DNA double-strand breaks in PAR1. This rearrangement may have been facilitated by the PAR1-specific chromatin architecture. The clinical features of the patient can be ascribed to SHOX haploinsufficiency and the presence of a 45,X cell line, although copy-number gains of some Yq genes and the size reduction of PAR1 may also contribute to his spermatogenic failure.
Journal Section:
Novel Insights from Clinical Practice
References
1.
Tuck-Muller
CM
, Chen
H
, Martínez
JE
, Shen
CC
, Li
S
, Kusyk
C
, et al. Isodicentric Y chromosome: cytogenetic, molecular and clinical studies and review of the literature
. Hum Genet
. 1995
;96
(1
):119
–29
. 2.
DesGroseilliers
M
, Beaulieu Bergeron
M
, Brochu
P
, Lemyre
E
, Lemieux
N
. Phenotypic variability in isodicentric Y patients: study of nine cases
. Clin Genet
. 2006
;70
(2
):145
–50
. 3.
Yang
Y
, Hao
W
. Clinical, cytogenetic, and molecular findings of isodicentric Y chromosomes
. Mol Cytogenet
. 2019
;12
:55
. 4.
Hattori
A
, Fukami
M
. Established and novel mechanisms leading to de novo genomic rearrangements in the human germline
. Cytogenet Genome Res
. 2020
;160
(4
):167
–76
. 5.
Liu
P
, Erez
A
, Nagamani
SC
, Dhar
SU
, Kołodziejska
KE
, Dharmadhikari
AV
, et al. Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements
. Cell
. 2011
;146
(6
):889
–903
. 6.
Stephens
PJ
, Greenman
CD
, Fu
B
, Yang
F
, Bignell
GR
, Mudie
LJ
, et al. Massive genomic rearrangement acquired in a single catastrophic event during cancer development
. Cell
. 2011
;144
(1
):27
–40
. 7.
Holland
AJ
, Cleveland
DW
. Chromoanagenesis and cancer: mechanisms and consequences of localized, complex chromosomal rearrangements
. Nat Med
. 2012
;18
(11
):1630
–8
. 8.
Baca
SC
, Prandi
D
, Lawrence
MS
, Mosquera
JM
, Romanel
A
, Drier
Y
, et al. Punctuated evolution of prostate cancer genomes
. Cell
. 2013
;153
(3
):666
–77
. 9.
Pellestor
F
, Gaillard
JB
, Schneider
A
, Puechberty
J
, Gatinois
V
. Chromoanagenesis, the mechanisms of a genomic chaos
. Semin Cell Dev Biol
. 2022
;123
:90
–9
. 10.
Lange
J
, Noordam
MJ
, van Daalen
SK
, Skaletsky
H
, Clark
BA
, Macville
MV
, et al. Intrachromosomal homologous recombination between inverted amplicons on opposing Y-chromosome arms
. Genomics
. 2013
;102
(4
):257
–64
. 11.
Abur
U
, Gunes
S
, Hekim
N
, Akar
OS
, Altundag
E
, Asci
R
. Clinical, cytogenomic, and molecular characterization of isodicentric Y-chromosome and prediction of testicular sperm retrieval outcomes in azoospermic and severe oligozoospermic infertile men
. J Assist Reprod Genet
. 2022
;39
(12
):2799
–810
. 12.
Ogiwara
Y
, Hattori
A
, Ikegawa
K
, Hasegawa
Y
, Kuroki
Y
, Miyado
M
, et al. Optical genome mapping for a patient with a congenital disorder and chromosomal translocation
. Cytogenet Genome Res
. 2022
;162
(11–12
):617
–24
. 13.
Lam
ET
, Hastie
A
, Lin
C
, Ehrlich
D
, Das
SK
, Austin
MD
, et al. Genome mapping on nanochannel arrays for structural variation analysis and sequence assembly
. Nat Biotechnol
. 2012
;30
(8
):771
–6
. 14.
Zhang
CZ
, Spektor
A
, Cornils
H
, Francis
JM
, Jackson
EK
, Liu
S
, et al. Chromothripsis from DNA damage in micronuclei
. Nature
. 2015
;522
(7555
):179
–84
. 15.
Acquaviva
L
, Boekhout
M
, Karasu
ME
, Brick
K
, Pratto
F
, Li
T
, et al. Ensuring meiotic DNA break formation in the mouse pseudoautosomal region
. Nature
. 2020
;582
(7812
):426
–31
. 16.
Liu
P
, Yuan
B
, Carvalho
CMB
, Wuster
A
, Walter
K
, Zhang
L
, et al. An organismal CNV mutator phenotype restricted to early human development
. Cell
. 2017
;168
(5
):830
–42.e7
. 17.
Hattori
A
, Okamura
K
, Terada
Y
, Tanaka
R
, Katoh-Fukui
Y
, Matsubara
Y
, et al. Transient multifocal genomic crisis creating chromothriptic and non-chromothriptic rearrangements in prezygotic testicular germ cells
. BMC Med Genomics
. 2019
;12
(1
):77
. 18.
Fukami
M
, Seki
A
, Ogata
T
. SHOX haploinsufficiency as a cause of syndromic and nonsyndromic short stature
. Mol Syndromol
. 2016
;7
(1
):3
–11
. 19.
Fukami
M
, Fujisawa
Y
, Ono
H
, Jinno
T
, Ogata
T
. Human spermatogenesis tolerates massive size reduction of the pseudoautosomal region
. Genome Biol Evol
. 2020
;12
(11
):1961
–4
. 20.
Saito
K
, Miyado
M
, Kobori
Y
, Tanaka
Y
, Ishikawa
H
, Yoshida
A
, et al. Copy-number variations in Y-chromosomal azoospermia factor regions identified by multiplex ligation-dependent probe amplification
. J Hum Genet
. 2015
;60
(3
):127
–31
. 21.
Mohandas
TK
, Speed
RM
, Passage
MB
, Yen
PH
, Chandley
AC
, Shapiro
LJ
. Role of the pseudoautosomal region in sex-chromosome pairing during male meiosis: meiotic studies in a man with a deletion of distal Xp
. Am J Hum Genet
. 1992
;51
(3
):526
–33
.22.
Lin
YW
, Hsu
LC
, Kuo
PL
, Huang
WJ
, Chiang
HS
, Yeh
SD
, et al. Partial duplication at AZFc on the Y chromosome is a risk factor for impaired spermatogenesis in Han Chinese in Taiwan
. Hum Mutat
. 2007
;28
(5
):486
–94
. © 2024 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2024
You do not currently have access to this content.
