Study confirms genetic link in cerebral palsy

Date:
October 7, 2020
Source:
University of Adelaide
Summary:
An international research team including the University of Adelaide
has found further evidence that rare gene mutations can cause
cerebral palsy, findings which could lead to earlier diagnosis
and new treatments for this devastating movement disorder.



FULL STORY ==========================================================================
An international research team including the University of Adelaide has
found further evidence that rare gene mutations can cause cerebral palsy, findings which could lead to earlier diagnosis and new treatments for
this devastating movement disorder.


==========================================================================
In the study published in the journal Nature Genetics researchers employed
gene sequencing to examine the DNA of 250 cerebral palsy families, and
compared this to a control group of almost 1800 unaffected families. They
then demonstrated the impact rare gene mutations can have on movement
control using a fruit fly model.

The findings have important clinical implications. They will provide some answers to parents, as well as guide healthcare and family planning such
as counselling for recurrence risk -- often quoted as around 1 per cent
but could be as high as 10 per cent when factoring in genetic risks.

Co-author of the research, Emeritus Professor Alastair MacLennan, AO,
at the University of Adelaide, says the new study confirms the pioneering
work of the Australian Collaborative Cerebral Palsy Research Group based
at the Robinson Research Institute at the University of Adelaide.

"Cerebral palsy is a non-progressive developmental movement disorder
impacting motor function, which affects approximately one in every 700
births in Australia and a similar number worldwide.

Symptoms range from mild to severe and can include intellectual
disability," Emeritus Professor MacLennan said.



========================================================================== "Historically, cerebral palsy was considered largely the result of
perinatal asphyxia -- decreased oxygen to the baby's brain at birth,
however this has only been in found in 8-10 per cent of cases.

"Eliminating other known causes, including premature birth and trauma at
birth, this leaves a large number of cases -- as many as 40 per cent in
some studies - - with an unknown origin." Researchers at the University
of Adelaide over many years have advocated that cerebral palsy is often
caused by rare genetic variations (or mutations) which disrupt a child's control of movement and posture.

"Where previous studies have indicated underlying genetic causes in
cerebral palsy, this study is the largest to date and includes in-depth statistical modelling and new controls to overcome limitations of earlier research," Emeritus Professor MacLennan said.

Co-author Professor Jozef Gecz, Channel 7 Children's Research Foundation
Chair for the Prevention of Childhood Disability and Head of Neurogenetics
at the University of Adelaide, says as a conservative estimate, 14 per
cent of cerebral palsy families in the study had an excess of damaging
genetic mutations and inherited recessive gene variations.



========================================================================== "Genes don't like to change; as soon as a gene is altered in any way you disturb its programing, and it can no longer perfectly perform what it's designed to do," said Professor Gecz, who is South Australia's Scientist
of the Year 2019.

"Our US collaborators were able to disturb the same genes in fruit fly as
found in humans, and in three out of four instances it severely altered
the movement of either fruit fly larvae or adults or both.

"The gene mutations were mostly spontaneous new variants occurring in
the sperm or an egg of the parents, who are otherwise not affected."
In some cases, identification of specific gene variations in individuals
in the study led to new recommendations for patient health management, including treatments that would not have been initiated otherwise.

"As little as 30 years ago we were very limited in treatments for
cerebral palsy, and the outlook for anyone diagnosed was grim," said
Professor Gecz.

"As we come to recognise the role of genetics in cerebral palsy, we
open the door for new treatments, earlier diagnosis and intervention,
which could lead to greatly improved quality of life." Other benefits of
the study include a potential reduction in litigation, and evidence for
further research to identify other damaging genetic variants in human DNA.

"The more we understand about the role of genetics in causing cerebral
palsy, the closer we get to learning how to prevent it," Professor
Gecz said.


========================================================================== Story Source: Materials provided by University_of_Adelaide. Original
written by Robyn Mills.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Sheng Chih Jin, Sara A. Lewis, Somayeh Bakhtiari, Xue Zeng,
Michael C.

Sierant, Sheetal Shetty, Sandra M. Nordlie, Aureliane Elie, Mark A.

Corbett, Bethany Y. Norton, Clare L. van Eyk, Shozeb Haider,
Brandon S.

Guida, Helen Magee, James Liu, Stephen Pastore, John B. Vincent,
Janice Brunstrom-Hernandez, Antigone Papavasileiou, Michael
C. Fahey, Jesia G.

Berry, Kelly Harper, Chongchen Zhou, Junhui Zhang, Boyang Li,
Jennifer Heim, Dani L. Webber, Mahalia S. B. Frank, Lei Xia,
Yiran Xu, Dengna Zhu, Bohao Zhang, Amar H. Sheth, James R. Knight,
Christopher Castaldi, Irina R. Tikhonova, Francesc Lo'pez-Gira'ldez,
Boris Keren, Sandra Whalen, Julien Buratti, Diane Doummar,
Megan Cho, Kyle Retterer, Francisca Millan, Yangong Wang, Jeff
L. Waugh, Lance Rodan, Julie S. Cohen, Ali Fatemi, Angela E. Lin,
John P. Phillips, Timothy Feyma, Suzanna C.

MacLennan, Spencer Vaughan, Kylie E. Crompton, Susan M. Reid,
Dinah S.

Reddihough, Qing Shang, Chao Gao, Iona Novak, Nadia Badawi, Yana A.

Wilson, Sarah J. McIntyre, Shrikant M. Mane, Xiaoyang Wang, David J.

Amor, Daniela C. Zarnescu, Qiongshi Lu, Qinghe Xing, Changlian Zhu,
Kaya Bilguvar, Sergio Padilla-Lopez, Richard P. Lifton, Jozef Gecz,
Alastair H. MacLennan, Michael C. Kruer. Mutations disrupting
neuritogenesis genes confer risk for cerebral palsy. Nature
Genetics, 2020; 52 (10): 1046 DOI: 10.1038/s41588-020-0695-1 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201007093625.htm

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