Skip to main content Accessibility help
×
Home
Hostname: page-component-79b67bcb76-f4n6r Total loading time: 0.248 Render date: 2021-05-14T11:36:04.984Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": false, "newCiteModal": false, "newCitedByModal": true, "newEcommerce": true }

P.075 Clinical spectrum of POLR3-related leukodystrophy caused by biallelic POLR1C pathogenic variants

Published online by Cambridge University Press:  05 June 2019

L Gauquelin
Affiliation:
(Toronto)
FK Cayami
Affiliation:
(Semarang)
L Sztriha
Affiliation:
(Szeged)
G Yoon
Affiliation:
(Toronto)
LT Tran
Affiliation:
(Montreal)
K Guerrero
Affiliation:
(Montreal)
F Hocke
Affiliation:
(Bordeaux)
RM van Spaendonk
Affiliation:
(Amsterdam)
EL Fung
Affiliation:
(Hong Kong)
S D’Arrigo
Affiliation:
(Milan)
G Vasco
Affiliation:
(Rome)
I Thiffault
Affiliation:
(Kansas City)
DM Niyazov
Affiliation:
(New Orleans)
R Person
Affiliation:
(Gaithersburg)
KS Lewis
Affiliation:
(Phoenix)
E Wassmer
Affiliation:
(Birmingham)
T Prescott
Affiliation:
(Skien)
P Fallon
Affiliation:
(London)
M McEntagart
Affiliation:
(London)
J Rankin
Affiliation:
(Exeter)
R Webster
Affiliation:
(Westmead)
H Philippi
Affiliation:
(Frankfurt)
B van de Warrenburg
Affiliation:
(Nijmegen)
D Timmann
Affiliation:
(Essen)
A Dixit
Affiliation:
(Nottingham)
C Searle
Affiliation:
(Nottingham)
N Thakur
Affiliation:
(Houston)
MC Kruer
Affiliation:
(Tempe)
S Sharma
Affiliation:
(New Delhi)
A Vanderver
Affiliation:
(Philadelphia)
D Tonduti
Affiliation:
(Milan)
MS van der Knaap
Affiliation:
(Amsterdam)
E Bertini
Affiliation:
(Rome)
C Goizet
Affiliation:
(Bordeaux)
S Fribourg
Affiliation:
(Bordeaux)
NI Wolf
Affiliation:
(Amsterdam)
G Bernard
Affiliation:
(Montreal)
DDD Study
Affiliation:
(Toronto) (Semarang) (Szeged) (Montreal) (Bordeaux) (Amsterdam) (Hong Kong) (Milan) (Rome) (Kansas City) (New Orleans) (Gaithersburg) (Phoenix) (Birmingham) (Skien) (London) (Exeter) (Westmead) (Frankfurt) (Nijmegen) (Essen) (Nottingham) (Houston) (Tempe) (New Delhi) (Philadelphia)
Rights & Permissions[Opens in a new window]

Abstract

Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.

Type
Poster Presentations
Copyright
© The Canadian Journal of Neurological Sciences Inc. 2019 
You have Access

Send article to Kindle

To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

P.075 Clinical spectrum of POLR3-related leukodystrophy caused by biallelic POLR1C pathogenic variants
Available formats
×

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

P.075 Clinical spectrum of POLR3-related leukodystrophy caused by biallelic POLR1C pathogenic variants
Available formats
×

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

P.075 Clinical spectrum of POLR3-related leukodystrophy caused by biallelic POLR1C pathogenic variants
Available formats
×
×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *