вход по аккаунту



код для вставкиСкачать
Journal of Diabetes and Its Complications 31 (2017) 1638
Contents lists available at ScienceDirect
Journal of Diabetes and Its Complications
journal homepage: WWW.JDCJOURNAL.COM
Variants m.13276G N A in the MT-ND5 and m.8241T N G in the MT-CO2
gene are not responsible for maternally inherited diabetes and deafness
Letter to the Editor,
We read with interest the article by Tabebi et al. about a Tunesian
family with maternally inherited diabetes and deafness (MIDD) 1
MIDD in case III/3 was attributed to the novel variants m.13276G NA
in the MT-ND5 and m.8241T N G in the MT-CO2 gene respectively. 1
We have the following comments and concerns.
Description of the neurological exam is misleading. The authors
mention that the neurological exam was normal but at the same time
they state that three family members (II/2, III/2, III/3) presented with
sensory-motor deficits. Surprisingly, clinical description in table 1 of
these three patients does not include sensory-motor deficits. 1 Which
were the results of the clinical exam in these patients? How many patients were diagnosed with MIDD? Among those with MIDD the neurological exam should not be normal since they had at least hypoacusis
and probably also diabetic polyneuropathy. How many of the family
members underwent nerve conduction studies (NCSs)? Were NCSs abnormal among the three patients with sensory-motor deficits?
Concerning the mtDNA variants found in these three patients, we
strongly doubt that any of the variants described was pathogenic. This
is because assessment of pathogenicity of the variants does not follow
standard procedures as proposed by the American College of Medical
Genetics (ACMG). 2 For example, variants m.8241T NG and
m.13276GN A have been reported independently only once. Only 100
control subjects were included. Only MITOMAP was checked for previous description of the variants. These variants were not found in the
mother and sister of the index patient, thus did not segregate with the
disease. No single fiber investigations and no cybrid studies, the golden
standard for confirming pathogenicity of a heteroplasmic mtDNA mutation, were carried out. There were also no biochemical investigations of
the muscle homogenate and no immune-histochemical investigations
of the muscle biopsy reported. With a score sum of 4 each, these variants have to be classified as benign according to the ACMG criteria.2
There are no conflicts of interest.
Both authors contributed equally.
No funding was received.
Author contribution: JF: design, literature search, discussion, first draft, SZ-M:
literature search, discussion, critical comments.
1056-8727/© 2017 Elsevier Inc. All rights reserved.
MIDD may phenotypically not only be restricted to diabetes and
deafness but may frequently present as mitochondrial multiorgan disorder syndrome (MIMODS). 3 Did the authors prospectively investigate
the family for subclinical manifestations other than the ones described
but frequently developing in patients with a mitochondrial disorder
(MID)? 4
In conclusion, this case study shows that confirmation of a mtDNA
mutation requires thorough genetic work-up to establish a strong genotype/phenotype correlation. Patients with MIDD need to be prospectively investigated for MIMODS.
1. Tabebi M, Charfi N, Kallabi F, Alila-Fersi O, Ben Mahmoud A, Tlili A, et al. Whole mitochondrial genome screening of a family with maternally inherited diabetes and deafness (MIDD) associated with retinopathy: a putative haplotype associated to MIDD
and a novel MT-CO2 m.8241TNG mutation. J Diabetes Complicat. 2017;31:253-9.
2. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines
for the interpretation of sequence variants: a joint consensus recommendation of the
American College of Medical Genetics and Genomics and the Association for Molecular
Pathology. Genet Med. 2015;17:405-24.
3. Finsterer J, Frank M. Maternally inherited diabetes and deafness is phenotypically and
genotypically heterogeneous. J Neuroophthalmol. 2016;36:346-7.
4. Finsterer J, Bastovansky A. Multiorgan disorder syndrome (MODS) in an octagenarian
suggests mitochondrial disorder. Rev Med Chil. 2015;143:1210-4.
Josef Finsterer
Krankenanstalt Rudolfstiftung, Vienna, Austria
Corresponding author at: Postfach 20, 1180 Vienna, Austria
E-mail address:
Sinda Zarrouk-Mahjoub
University of Tunis El Manar and Genomics Platform
Pasteur Institute of Tunis, Tunisia
Без категории
Размер файла
139 Кб
2017, 002, jdiacomp
Пожаловаться на содержимое документа