short stature as the only presenting feature in a patient with an isodicentric (y)(q11.23) and...

5
ORIGINAL PAPER Jacques C. Giltay á Margreet G. E. M. Ausems á Ineke van Seumeren Richard A. Zewald á Richard J. Sinke á Brigit Faas á Monique de Vroede Short stature as the only presenting feature in a patient with an isodicentric Y)q11.23) and gonadoblastoma. A clinical and molecular cytogenetic study Received: 12 July 2000 / Accepted: 20 September 2000 Abstract A 13-year-old phenotypically female patient presented with short stature height SDS ±2.6), but without any Turner stigmata or other dysmorphic features. Chromosome analysis showed mosaicism for an isodicentric idic) Y)q11.23) containing cell line and a 45,X cell line. Subsequent gonadectomy revealed a left streak ovary and a right ovary of abnormal appearance, which on histological examination appeared to contain a gonadoblastoma. DNA analysis showed that the proposed critical region of the gonadoblastoma locus on the Y chromosome was contained within the patient's idic Y). Conclusion The case described here shows that patients with 45,X/46,X, isodicentric Yp) mosaicism and a female phenotype 1) can lack external virilisation but still have a gonadoblastoma and 2) do not necessarily have Turner stigmata but can present with only short stature. This case also underlines the importance of karyotyping patients with unexplained short stature to enable gonadectomy if Y-derived material is detected. Key words Cytogenetics á Gonadoblastoma á Isodicentric Y chromosome á Short stature á Turner syndrome Abbreviations DAZ deleted in azoospermia á FISH ¯uorescence in situ hybridisation á GBY gonadoblastoma locus on the Y chromosome á idic isodicentric á SRY sex determining region on the Y chromosome á STS sequence tagged site Introduction Short stature is one of the main clinical features of Turner syndrome either in its mosaic or non-mosaic form. Turner syndrome is associated with a 45,X kary- otype in approximately 50% of cases. In mosaics the most frequently found second cell lines have a 46,XX or a 47,XXX karyotype [12], and a second cell line con- taining Y-derived material can be detected in a few cases. Phenotypic females with Y chromosomal material have an increased risk for gonadoblastomas. This risk is thought to depend on the presence of a gene or genes) referred to as gonadoblastoma locus on the Y chromo- some GBY) [10]. GBY has been mapped to a 1±2Mb pericentromeric region of the Y chromosome [14, 16]. Since the majority of such females have been shown to carry an intact Y chromosome, mapping of the critical region for GBY has relied on molecular investigations in patients with structurally aberrant Y chromosomes. Eur J Pediatr 2001) 160: 154±158 Ó Springer-Verlag 2001 J. C. Giltay &) á M. G. E. M. Ausems á R. A. Zewald R. J. Sinke á B. Faas University Medical Centre Utrecht, Department of Medical Genetics, KC.04.084.2, PO Box 85090, 3508 AB Utrecht, The Netherlands e-mail: [email protected] Tel.: +31-30-2503800; Fax: +31-30-2503801 I. van Seumeren Department of Obstetrics, Neonatology and Gynaecology, AB Utrecht, The Netherlands M. de Vroede Department of Child Endocrinology, The Netherlands, AB Utrecht, The Netherlands

Upload: monique

Post on 25-Aug-2016

217 views

Category:

Documents


2 download

TRANSCRIPT

Page 1: Short stature as the only presenting feature in a patient with an isodicentric (Y)(q11.23) and gonadoblastoma. A clinical and molecular cytogenetic study

�������� ����

������� � �� �� � ������� � � ������ � ����� ��� ��������������� � ������ � ������� � ����� � ����� ��� � �!����� �� "�!���

����� ������ �� �� ��� ����� ����� � � �������� � ���������� ����������� �� ��������������� ������� �� �������� �������� �����

��� �� �� ���� ���� �������� �� ������ ����

�#� ��� � ���� ��!�� �"#!����� ��� $� � � ��#� ��%#�� &��" %"!�� %� ���'"�("� �)� *�+,-. ��� &��"!�� #� /��#� %��(� � !� !�"� ��%�!��"�� $ ���%+0"�!�!%!� # ��%�% %"!&� �!% ���%� $!� # �%!���#���� '����- '1-'2��+��- �!#� �#�#(��� ��# #� 34.5 ��� ��#+ ���%2�#� (!# ���!�� � �� �$� %�� 6 ! �� #� ��("� ! �� !$ �#!�� � �� � #�. &"��" !# "�%�!�!(�� � 7 ��# ��!# �� �� �!�!#� �# (!# �!�� %�!� + )�� # ��%�% %"!&� �" � �" ��!�!%� ������ � �(�!# !$ �"(!# �!�� %�!� �!��% !# �" 1 �"�!�!%!� & % �!#� �#� &��"�# �" � ��#�8% ���� '1-+

�!������!� /" � % �%����� "� %"!&% �" � � ��#�% &��" 34.5�3,.5. �%!���#����'1�- �!% ���%� #� $� � �"#!��� '�- � # � �6 7��# � �����% ��!# ��� %���� " (!# �!�� %�!� #� '�- �! #!� #�%% ���� " /��#� %��(� � ��� � # ��%#� &��"!#�� %"!�� %� ���+ /"�% � % �%! �#����#% �" ���!�� #� !$ 6 ��!����#( � ��#�% &��"�#7�� �#� %"!�� %� ��� �! # �� (!# ���!�� �$ 1���� � � ��� � �% �����+

$�� �!��� 0��!(#���% � �!# �!�� %�!� � �%!���#���� 1 �"�!�!%!� ��"!�� %� ��� � /��#� %�#��!�

�##����� �!�� ��� ���� �# 9!!%���� � ���� :�!�%�#� �# %��� "������% ��!# �� (!# �!�� %�!� �!��% !# �" 1 �"�!�!%!� � ��� �%!���#���� ��� %7 �����#�#( �(�!# !# �" 1 �"�!�!%!� � ��� %2�#� � ((� %��

����������

�"!�� %� ��� �% !# !$ �" � �# ���#�� � $ ���% !$/��#� %�#��!� ��"� �# ��% �!% �� !� #!#��!% ��$!��+ /��#� %�#��!� �% %%!�� �� &��" 34.5 6 ���!��� �# ���!7�� ��� 4�; !$ � %%+ �# �!% ��% �"�!%� $�2�#��� $!�#� %�!#� ��� ��#% " 3,.55 !� 3<.555 6 ��!��� =��>. #� %�!#� ��� ��# �!#�� �#�#( 1���� � � ��� � � # � ����� �# $&� %%+

�"#!����� $� �% &��" 1 �"�!�!%!� � � ��� �" # �#�� %� ��%6 $!� (!# �!�� %�!� %+ /"�% ��%6 �%�"!�("� �! ��#� !# �" ��%#� !$ (# '!� (#%-�$��� �! % (!# �!�� %�!� �!��% !# �" 1 �"�!�!�%!� '�?1- =��>+ �?1 " % �# � ��� �! �*�@�����#��!���� �(�!# !$ �" 1 �"�!�!%!� =�3. �,>+��#� �" � A!���� !$ %��" $� �% " �# %"!&# �!� ��� # �#� �� 1 �"�!�!%!�. � ���#( !$ �" ������ ��(�!# $!� �?1 " % ���� !# �!���� � �# %��( ��!#% �#� ��#�% &��" %������� ��� ��� #� 1 �"�!�!%!�%+

�� � ��� �� '����- �,�� �43*�4B � ����#(��C�� ( ����

�+ 0+ ���� � '�- � @+ �+ + @+ ��%�% � �+ �+ D& ���+ �+ ��#6 � ?+ E %F#� �%��� @��� � 0#�� F���"�.)� ���#� !$ @��� � �#���%.G0+�3+�B3+�. �� ?!7 B4�H�. �4�B �? F���"�./" ��"�� #�%�� ��� �+0+���� �I��(+ 9�+#�/�+� J�������4��B��K E 7� J�������4��B��

�+ # ����#)� ���#� !$ ��%�����%. �!# �!�!(� #� ��# �!�!(�.�? F���"�. /" ��"�� #�%

@+ � C�!�)� ���#� !$ 0"��� #�!���#!�!(�. /" ��"�� #�%.�? F���"�. /" ��"�� #�%

Page 2: Short stature as the only presenting feature in a patient with an isodicentric (Y)(q11.23) and gonadoblastoma. A clinical and molecular cytogenetic study

L!& �. !#�� $& ��!��% !$ �!���� � %����% �# %��"� ��#�% " �# �����%"�+

/" ���#�� � ��%#� ��!# !$ � ��#�% &��" # �%!����#���� '����- '1- � # � /��#����6. �#��%7���6 !�� � =<. ��. �<>+ � M#!�� �8 $� � �"#!��� �# %��"� ��#�% �% ��!� ��� � �+

N ��%#� �"#!����� ��� $� � � ��#� &��"%"!�� %� ��� #� �!% ���%� $!� # ���� '1- ��� � �6 !$ #� 7��# � �����% ��!#. &"! " � (!# �!�� %�!� +/" $!��!&�#( �# %��( ��!#% &� � ���� !�� �# !��� �!�#��%� #� �" �� �#� ��%��� #�� ��&# �"#!���� #� (#!���+ �#���" % :�!�%�#� �# %��� "�������% ��!# 'E��L- !# �" (!# �% & % ��$!��� �!%���� ��%%��%���O� �!% ���%�+ )�� %����% &� ���$!��� �! �# %��( � &"��" � ��% !$ �" 1 �"�!�!%!�&� ��%#� #� &"�"� �?1 & % �!#� �#� �# �" ����'1- �� �O#�#( ��% �� 6�!�#�+

�� � ���

/" � ��#� & % �$��� � ��+4 � �% !$ ( �� �% !$ %"!��%� ���+ �" & % �" O�%� �"��� !$ #!#��!#% #(��#!�%. " ��"�� �#�%+ L� ����" �#(�" & % 4� �� '�4�- #� %" &�("��+�B� 6( '�4�-+ L� ���� � "�%�!�� & % �#�� �6 �� 7��� $!������#� �#$���!#% !$ �" ���� �%��� �!�� �� ��+ �%��"!�!�!�� �!��#� & % #!�� �+

�"�%�� � 7 ��# ��!# � �� #!�� � �!!6�#( (��� &��"!��/��#� %��(� � . � �� $�!� %"!�� %� ��� '�33 ��. "�("� �)� *�+,K � ��# � "�("� �,< ��. � ��# � "�("� �,< ��. � �(� "�("��,4 �� !� �)� *�+B4- =�>+ /" 7��# � (#�� �� &� #!�� �+/"� & % �� %� �����#( #� %� #�� ����� " ��+ /"� &� #!�# � !� � ��� � �$��%+ L� �!# ( & % �� � �% #� , �!#�"% ��!���#( �! ������" #� ��� =4>+

� �!� �!�� �# %��( ��!#% %"!&� � �� %��� � �% !$ E�L'��H F��- #� �L '�< F��-. #!�� � %��� � �% !$ �%�!%��!#'�+H< #�!���-. #��!%�#��!# '�+, #�!���-. ��"���!�� #��!%���!# '�3 #�!���- #� �!& %��� � �% !$ !%�� ��!� ',4 ��!���- #�!%��!# '�34 ��!���-+ /"��!�� $�#���!# #� %��� �#%���#���6(�!&�" $ ��!��� � �% &� #!�� �+

�$�� ���!(#��� �����!# !$ 1���� � � ��� � '% �%���%-.�� �� ���� %!#!(� �"� & % ��$!��� &"��" ��%��!%� # �#$ #�������% #� �&! %� �� ! ��%+ ���%2�#���. � � �!%�!��� (!# ����!�� & % � ���� !��+ @ ��!%�!��� ��� �" ��("� ! �� " � # �#!�� � �� � #�. &"� % �" �$� !# & % �� ��� %�� 6! ��+ L�%�!�!(�� � �# %��( ��!# � �� (!# �!�� %�!� #�����( ��� %�������% �# �" ��("� (!# �+

/" � ��#� & % �� �� &��" ��!���# #� "�� # (�!&�" "!���!# '3 �F���-. ��!���#( �! �" (�����#% $!� /��#� %�#��!� #� �!& �!%% !$ ����!#�%� !%��!(# '�<���!%�� ��!� %� �� �!%�+��4 �(�6( �� � �-. &"��" & % �#�� %� %� ����+

�� �,+4 � �% !$ ( "� ����#� "�("� �% �4<+4 �� '"�("� �)���+<-+ �" " % $��� �� %� � �!��#� '/ ##� %� ( 4-. #� #!��� � ����� " �� '/ ##� %� ( 4-+ ?!# ( & % � � � �� � �% #�, �!#�"% '"�("���!# ( �)� ��+�-+ �% ��. �"� �% #! �#��� ��!#!$ ���!�� �����#�+

!������� �� ������

0��!(#��� �# %��( ��!# #� :�!�%�#� �# %��� "������% ��!#

@� �" % %�� �% !$ �"��!" � ((����#�#�%����� �� ����"� �����"!���% &� ��� �� �# ��!�� #� &��" %� #� �� ��!�����%+ 0"�!�!%!�% &� # ��%� $�!� ��� #�� ��� � ��!#%+E��L & % ��$!��� % �%����� �� �!�%�� =�>+ �� %��� ��!�

E��4���. &"��" �% %���O� $!� 1� =�H>. & % ��!��#�� ���� #������ �� ���#�E�/0 =�>+

�#���" % :�!�%�#� !# �" (!# �%

� � P#�O7� %���% $�!� �" �$� #� ��("� (!# �%. �#�����#( ��A �#� ��� . &� �%� $!� �#���" % E��L. &"��" & % � ���� !�� % �%����� =,>+ )������ � ���� ��!�% %���O� $!� �" 5 #� �"1 �"�!�!%!�% 'C�%�%- &� �%�� %������ !� #(�� �����#��!�� 1 ��!� '0� 1- #� %������ (�#�� ���� �#���!�� 5 ��!� '0� 5-+ ��#� �#���" % E��L !# ��%%� %���!#%�����% �" � %�(# �% � # � ��%%� %����� �� �% �" � �� !$ �" ����!#� �#�#( �" �"�!�!%!� �! &"��" �" ��!� �% ������ �% ��� !Q #� �"�$!� #!� ��%#� !# �" %���. & $�� �" � �� & % #!� ��(���� � �! (� �!� �" # A�%� �!�(" %��� � !$ �" ��%�������!#!$ �" %�(# �%+

)�� # ��%�%

�#!��� )�� & % �%!� �� $�!� ����"� � ��!!�. �%�#( %� #� ����!����%+ �0� # ��%�% !$ �4 ��Q�#� 1 �"�!�!%!� %���O�.%2�#� � ((� %�� '�/�- ��!�% =��. �B> & % �"# � ���� !�� �!���� �" ��%#� !$ ��Q�#� �(�!#% !$ �" 1 �"�!�!%!�+/���� ���. �" � ���!# �!#� �#� ��� #( (#!��� )��. ��� #($!�& �� #� � �% �!��%�%���O� �����% �# O# � !��� !$ �4 ���!#� �#�#( �+�4 �#��% / 2 �!���� % '��6�#����. 0��%-.�+4 �@ ��/�. ��; )@��. �+�4 �(��� ?��. ,< �@ /��%�L0��L B+B. ,+< �@ @(0��. �� �@ ����� ��!�" #!�. ,+< �@ � ��)/� #� �,+, �@ '�L3-���3+ /" % ���% &� �# ���� �H3 �0 $!� 3 ��#. $!��!&� �� �� ����% !$ �# ��� ��!# 'H� �0.�� %+-. ## ��#( '44 �0. � ��#- #� 7�#%�!# '<� �0. � ��#+-+���2�!�% '�� ��- !$ �" �%����#( �0� ��!����% &� # ��%� !# �; ( �!% (�+

"�����

0"�!�!%!� # ��%�% � �� �!% �� 34.5.�# '��-�'���+�2��+�-�3,.5.����'1-'2��+��-.�# '��-'���+�2��+�-�3<.5.����'1-'2��+��-7�. �# '��-'���+�2��+�- 6 ��!���'E�(+ �- �# � ��! !$ ���3<�4+ �# �� �� ����"!��������� �"�% � ��! & % B�3���+ /"�% ,3; #� B3; !$ �"���% $�!� �" �%���� ����"!��� ������% �!#� �#� �� %� !# ���� '1-+

E��L �!#O��� �" ��%#� !$ �&! 1 �"�!�!%!� �%"!�� ��% �# �" ���� '1- &��" ��!� %���O� $!� 1�'E�(+ �-+ /" ��%� � $� (�#� �#�����#( �" :�!�%�#�"��!�"�!� ��# !$ �" �!#( ��% & % ��%%�#(+ )��

�� % /&! 7 ���% !$ �" � ��#�8% ��� #�� �)�0 '1-'2��+��- #� ���!(� �%+ �# ����� �#��� �% �" �� 6�!�#�

�44

Page 3: Short stature as the only presenting feature in a patient with an isodicentric (Y)(q11.23) and gonadoblastoma. A clinical and molecular cytogenetic study

%����% &� ��$!��� �! $���"� �O# �" �� 6�!�#�'% ��!&-+ /" ����#���� �# �%�!# !$ �"�!�!%!� ��& % �#"���� $�!� �" $ �"�. %! & �( �� �� % ����� #� �! �" �"#!��� !$ �"�% � ��#�+ �� �� $�!� �"�%� ��# � �# '��-. �" � �#� � 6 ��!���% &� #!�� �+/" ��%#� !$ �&! ���� '1- �"�!�!%!�% �# %!� ���%' % �# �"�% � ��#�- �% �"#!�#!# &"��" �% ��!� ����� �! �" 7�%�#� !$ �&! �#��!��% �# �"% �"�!�

�!%!�%. !# !$ &"��" � � #!� � #����� �# ��� ��.�#�� %�#( �" ��%6 !$ ���!��� #!#���%A�#���!# =3>+ ��%���#�� � %�(#�O� #� �% �#�� �+

/! %���� �# �!� �� �� &"��" 1 �"�!�!%!� � ��(�!#% &� ��%#� �# �" ���� '1-. & ��$!��� ��������7 �0� # ��%�% !$ 1 �"�!�!%!� %���O� �/�%��%������� �"�!�("!�� �" 1 �"�!�!%!� �!��%�!#���#( �! �" �#�� �% �� �! ,) 'E�(+ �-+ /"% �#�� �%&� %"!&# �! � ��%#� �# �" ���� '1- �# ��!�� #�&��" �" �!� ��% ��!# !$ �" �?1 ������ � �(�!# # � �"�#��!�� !$ �" 1 �"�!�!%!� �# �" �(�!# �!#%�%���#( !$ �" �#�� �% � �! 4 =�3. �,>+ �/�% �!���%�!#��#( �! �" ���� �# 9!!%���� ')�D- �!��%&� �%#�. &"��" �� �% �" �� 6�!�#� ��!7�� � �!�" ,) �#�� � 'E�(+ �-+ /"�%. �" ���� '1- �!#� �#% �"�"�!�!%!� � � ��� � !$ ��!%� �&! 1 �"�!�!%!�%� �6�#( %� �� 12 ��%� � � ��+

��#� �" � �!��#� !$ (!# �!�� %�!� ��#�%!# �" ��%#� !$ �?1. & "��!�"%�%� �" � �" ����#� ( !$ ���% �!#� �#�#( # ���� '1- ��("� � #"�("� �# �" (!# �% �" # �# �" ����"!���%+ N�"�$!� ��$!��� �#���" % E��L !# � � P#�O7�%���% !$ �!�" (!# �% #��!� �" �A �#� ��� &��"��!�% %���O� $!� �" 5 #� 1 �"�!�!%!�%+ L!& �.�" ���#� ( !$ 1��!%��� ���% �# �"% ��%%�% ��� #!�%� �! ��Q� %�(#�O� #��� $�!� �" � !$ ���� '1- �!#�� �#�#( ����"!���% '� � #!� %"!&#-+

#��������

/" �!�#( $� � �# �"�% ��!�� & % �# %��( �� $!�%"!�� %� ��� #� �� �� �! " "���(!# �!��!���"��!(!# ��%�. �!% ���%� $!� ��� ��# �!#� �#�#( #

�� & E��L &��" ��!� 'E��4���- %���O� $!� �!��% !# �"%"!�� �� !$ �" 1 �"�!�!%!� %"!&% �&! %�!�% '�����-.�!#O���#( �" � �" �)�0 '1- �!#� �#% �&! %"!�� ��%

�� ' �%���% !$ �" 1��"�!��!%!� %���O� �/� # ��%�%+�% �$�#� # ���!(� � !$�" 1 �"�!�!%!� �% �#������#��� ��#( �" �?1 ������ � ��(�!# #� �" ��!�% �%� $!�E��L !# ����"!���% 'E��4���- #� !# � � P#�O7� %���%!$ �" (!# �% '0� 1-+ /"%"!�� �� '�-. �" �!#( �� '2- #� �" "��!�"�!� ��# �(�!# � �%! �#��� ��

�4,

Page 4: Short stature as the only presenting feature in a patient with an isodicentric (Y)(q11.23) and gonadoblastoma. A clinical and molecular cytogenetic study

���� '1- #� 34.5 ��� ��# �# ����"!���% #� (!# �%. #� (!# �!�� %�!� �# !# !$ �" (!# �%+

�% $ � % & 6#!&. �"� � #! ��!��% !$ #� � ���#� &��" �"�% ��� !$ �!% ���%� ��� � �6�#( /��#�%��(� � #� %�(#% !$ �����% ��!#. #� ��%#��#( &��" (!# �!�� %�!� + /&! ��#� � %% &� �%����� &��" %���� � �!% ���%� =�. H> #� !# &��" # ���� '1-�!#� �#�#( # # � �(� $� (�#� !$ 12 '�#�����#()�D- ��� �� �"% � ��#�% ��%#�� &��" /��#�%��(� � . #! �����% ��!# #� #! ��#� !$ (!# �!��� %�!� =B>+ �!��#%!# � �+ =��> %����� �3 � ��#�%&��" %������� ��� �#!�� � 1 �"�!�!%!�% #� %"!&��" � �# % # !�� !$ �# � ��#�% &��" # ���� '1- %���� ��! �" !# �# !�� � ��#� �" �� 6�!�#� & % �# 12��&# �#�� �% ,�*? #� <. &"��" O�% �! �" �� 6��!�#� �(�!# & �O#� '��&# ,� #� )-+ ?�� �%!�"% � ��#�% &� �� %��� �#� �� �% �"� " �/��#� %�#��!�+

���!���#( �! L%� =<>. �" !�����#� !$ /��#� %��(�� � �# � ��#�% &��" 1 �"�!�!%!� �#!�� ����% �%�� �� �! �" ��%#� #� � � !$ �!#����#� 34.5��� ��#+ �# !�� � ��#� �� �� ����"!��� ������%%"!&� �" � �,; #� �,;. �%���� ��. !$ �" �����"!���% " � �" 34.5 ��� ��#. �� �"� &� #! /��#�%��(� � + ���" � �6 !$ /��#� %��(� � 7��� $!�%"!�� %� ��� #� (!# � � ��%$�#���!# & % �%����� �#�� !�� !$ B� � ��#�% &��" �!% ���%� $!� # ���� '1-�� ��#( ��� ��# =�<> ��� �" ��%�������!# !$ �" � ������� ��#( ��� ��#% & % #!� �#��!#�+

/" !�"� �#��%��#( $ ��� �# !�� � ��#� �% �"!�����#� !$ (!# �!�� %�!� �%��� �" �!���� �%#� !$ �����%�#( %�(#%+ N &!#��� &"�"� �"��%%� ��%�������!# #��!� %������� � $ ���% !$ �" ����'1- �!��� 7�� �# �"�%+ �# � � %� ,3; !$ �" ���% 7� ��#� $�!� !�� � ��#�. # ���� '1- & % ��%#�+ �0� # ��%�% !$ ����"!����� )�� %"!&� �� �!#� �#� �"�"�!�!%!� � � ��� � !$ ��!%� �&! 1 �"�!�!%!�%.� �6�#( %� �� 12 ��%� � � ��+ ��#� �" �� 6�!�#� !$�" ���� '1- �% �# �" �!#( ��. �"� %"!��� � # �#� �������� �� %"!�� �� !$ �" 1 �"�!�!%!� �!#� �#�#(�" %7 �����#�#( �(�!# !# �" 1 �"�!�!%!� '��1-�!��%+ ���!���#(�� #!�� � �0� ��!���� !$ �" ��1�!��% & % !�� �#� 'E�(+ �-+ @�#!� %������� � �#!��� ����% �# �" ��1 �(�!# � ##!� � 7����� ��� %��" ��� ��!#% �� � 2��� �#�%� � #� �"�$!� ��!� ����! #!� 7�� �# �" �%#� !$ �����% ��!# =�4> �# ���� '1-� ��#�%+

������%�#(��. &"� % �" ��%#� !$ � A!� � ��% !$�&! 1 �"�!�!%!�% ��� #!� �%��� �# �����% ��!#. (!�# �!�� %�!� & % $!�#� �# �" (!# �% !$ !�� � ��#�+/" �?1 ������ � �(�!# & % %"!&# �! � ��%#� �# �"���� '1- �"�!�!%!�+ 1� �" ���#� ( !$ 1 �!%��� ���% �# �" (!# �% �� �� �! � %���� � �! �" � �# �"����"!���%. ����#( !�� �" � "�("� �! � !$ ���� '1-��!#� �#�#( ���% �# �" (!# �% � �%� �" � �!��#� !$�" (!# �!�� %�!� �# �"�% !�"�&�% �# �����%� � ��#�+/" ��%�������!# !$ �" �!% �� ��� ��#% �# ��Q�#� ��%�%�% '#!� !#�� ����"!���% #� (!# �%- �# �"% � ��#�%�% ��!� ��� �" �!%� ���!�� #� $ ��!� �# �����#�#( �"

�"#!����� !���!�. &"��" ��("� � #!�� � $� �./��#����6. ���(�!�% !� � �+

/"�% � % ��!�� �% # 7 ��� !$ �" !�����#� !$ (!# �!�� %�!� �# %� �� ��� !�"�&�% #!�� � �#��� ��� �+ /"�% �% �# $ �� �" � A!� �!#��# �# �"%� ��#�%. %�#� (!# �!�� %�!� � � �!�#�� ���� ��(# #� ���!��% $!� &"��" �� #�� (!# ���!���% ��!��#��+ ��� � % ��!�� �"�$!� ��" %�%%!#� ( �# �" � (���% &��" �#7�� �#� %"!�� %� ����%� $���"� �# %��( ��!# �#�����#( �"�!�!%!� # ��%�%+

����!��������� N �" #6 �+ G �% #� + /!��6#% $!� �"��7��� ��"#�� � %���!��+

"����

�+ �%%����R ! ��. L �6� 0. @ �2�%���E �� ��. ) @��!@� '����- @!���� � � ���#( !$ # ����'1�- �"�!�!%!� �# # F�����"�/��#� � ��#�+ �� � @� �#� H�� H4*HB

�+ E����6% �@. # ?���# �. ?��(��A� ��E. C��!! �C #"!���6 ��. N�� �@ '�HH<- ���� #�% (�!��� (� ��#�HH< �# "�%�!��%�" ��%����$ '�# )���"-+ �#� N�� �@ '�- ) ��� � #���A6 (�!�%����+ ?!�" 0!���%%�. ���#.�� �*��

�+ ���� � �0. ?!6� ��. � E� #� L. ?�� E� '�HHB- C�)."��!%� �� % #� #!�� � �%��"!�!�!� � �!��#� �# � ��#�&��" �# ��� B'2���2��+�-+ 0��# �#� 4�� <3*<B

3+ ��� �� E. @ ��� �E. ��� % 0. @ ��� @� '�H<<- E!��#& � %% !$ ���#���� 1 �"�!�!%!�%+ L�� �#� �,� �3H*�,�

4+ ������" NN. ��� �� '�H4H- � ��!(� �"�� �� % !$ %6�� �� �!��#� !$ �" " #� #� �" &��%�. �#� �#+ �� #$!��F#� �%��� ��%%. �� #$!��

,+ L!�� # �L. # L!!�# . # � G 0�. C!!�A% ��.� � 6�% E0 '�HH�- )����!# !$ #����� � �"�!�!%!� ��� ��!#% �%�#( �# %��� "������9 ��!# �# � � P# %���!#% !$�!���#�� ��!�%%� �� ��� � #��%+ @!� � �"!� 3� 4��*4��

<+ L%� �1E '�HH3- �"#!����6 ��!��� �!��� ��!#% !$ 1�"�!�!%!� #���!��� &��" ��" %�% !# %������� � ��� ���!#% �# �!%��# � ��� �� (#!%� � %%+ �� � @� �#� 4�� ��B*�3�

B+ �#��#� �. ��"���� N. L�� G� '�HHB- ��%#� !$ �"�DE �(�!# �# $� � &��" # ����'1-'2��-+ 0��# �#� 43��3�*�33

H+ @!� . L�� ## �. 09 6!S @. �!��S %9 �. G!%9�!� S �'����- �%!���#���� 1 �"�!�!%!� �# # F�����"�/��#� � ��#�&��"!�� �����9 ��!#+ �� � @� �#� H�� HH*���

��+ � ( )0 '�HB<- L��!�"%�%� 1��"�!�!%!� � (# � �%%(!# �!�� %�!� �# ��%(#��� (!# �%+ ) �!��#� ���=������>� �4�*�44

��+ ��A! �. � /�1. � �! �. �� ( �� # �. ?�!&# ��. �!%#��(@. �!9# �. � Q /. ��� �% ). L! �� �. ) � 0" ��� �.����� �. � ( )0 '�HH4- )� �% %��� �!(#�� �$��% �#"�� #% � �%� �� 1 �"�!�!%!� ����!#% #�!�� %%�#( #! � ������#��#( ��!��# (#+ � � �#� ��� �B�*�H�

��+ �!��#%!# �. � � 0" ���� � '�HH4- �7 �"�!�!%!� �#!�� ����%+ �#� ��� #� ���!�# ) '�%- ���#����% #��� ���� !$ ���� � (#���%. ��� �#+ 0"���"��� �� �#(%�!#. ��H<�*HB�

��+ �!��#%!# )�. ) ��!# �. � �!�% ��. @!%% G. �!&� @@.�6�% )L. 0�!�� �� '�HHH- � �!���� � #� E��L # ��%�% !$%������� ��� �#!�� � 1 �"�!�!%!�% �# � ��#�% &��" /��#�%�#��!�+ � @� �#� �,� �<H*�B3

�3+ � �! �. G �� �## L. ���! �� C. ���!� 6� �. � ( )0. � � 0" ��� � '�HH4- @!���� � � ���#( !$ �" ��� �� (!# �!��� %�!� �!��% !# �" 1 �"�!�!%!�+ �#% 0"�!�!%!�%0 #�� �3� ���*��3

�4<

Page 5: Short stature as the only presenting feature in a patient with an isodicentric (Y)(q11.23) and gonadoblastoma. A clinical and molecular cytogenetic study

�4+ ������ �. 0 � ��% �. E� #�"� ��. @�#( ���� �. @!��9�! .� � ��#! �. � �6 � '�HH,- @!���� � %����% �# �"� � ��#�%&��" �%!���#���� 1 �"�!�!%!�+ L�� �#� HB� ,H�*,H4

�,+ /%��"�� G. ��A! �. � ( )0. )�%��" 0@ '�HH4- �!# �!��� %�!� � �!���� � �O#���!# !$ �" %�%���������� �(�!# !#�" 1 �"�!�!%!�+ �� � L�� �#� 4<� �3��*�3�<

�<+ /��6�@���� 0@. 0"# L. @ ���#9 �. �"# 0�0. �� �.G�%�6 0. ? ��%� )�5. ?" �# ( � 1@. )!&��#( . N����6�N '�HH4- �%!���#���� 1 �"�!�!%!�� ���!(#���. �!���� � #� ���#�� � %����% #� � �& !$ �" ���� ���+ L�� �#� H,���H*��H

�B+ C!��� �" ). E!!� �. L���!# �. ?�!&# ��. ?���!� #! �.?!( # ��. � ( )0 '�HH�- /" "�� # 1 �"�!�!%!�� 3���#�� � � � � %� !# # ��� ��� !������#( ����!#%+ ���#��4B� 4�*4H

�H+ N ��� E. ��"�� �. E� �� �! @. L�%��#7 /N�. N�%%#� �"�. N�� #� �. @ ��! �. ? �6 . N!�$ F '�HB<- ��%#� !$1�%���O� )�� %2�#�% �# "�� # 3,.55 ��� "�� �"�!����% #� �# 34.5 ��7� (!# � � ��%(#%�%+ L�� �#� <,����*��,

�4B