DUPLICATION OF CHROMOSOME 16p13.11-p12.3
WITH DIFFERENT EXPRESSIONS IN THE SAME FAMILY
Pop-Jordanova N1,*, Zorcec T2, Sukarova-Angelovska E2, 3
*Corresponding Author: Professor Nadica Pop-Jardonica, Department of Medicine, Research Centre
for Genetic Engineering and Biotechnology “Georgi D. Efremov,” Macedonian Academy of Sciences
and Arts, Bul. Krste Misirkov 2, 1000 Skopje, Republic of North Macedonia. Tel.: +389-2-32-35-400.
Fax: +389-2-32-35-423. E-mail: popjordanova.nadica@gmail.com
page: 89
|
|
CASE REPORT
The proband, MG, female, first came to the University
Children’s Hospital, Skopje, Republic of North Macedonia
(RNM) 4 years ago, at the age of 2.5 years, with suspected
developmental delay (DD). Clinical observation confirmed
speech and language difficulties (absence of expressive
language and poor receptive language), poor nonverbal
communication, poor gaze phenomena, not responsive
to her own name, very poor social skills and interaction,
many stereotyped behaviors, sensory difficulties, poor play
skills and poor general knowledge. She was diagnosed
as being autistic, according to the criteria for autism described
in the Diagnostic and Statistical Manual of Mental
Disorders, 5th edition (DSM-5) [1]. She started receiving
therapies from the special educators and rehabilitators,
speech and language therapists and psychologists such
as sensory integration, speech therapy and psychomotor
reeducation. At the hospital, she still receives treatments
with joint attention, symbolic play, engagement regulation
(JASPER) and discrete trial training (DTT). Preschoolbased
JASPER intervention in minimally verbal children
with autism, is highly recommended and provides good
results [7]. Additionally, DTT is a structured technique
that breaks down skills into small, “discrete” components.
Systematically, the therapist teaches these skills one by one
[8]. At some point of the treatment, she received medications
such as Risperidone (antipsychotic) and Nootrop
(stimulant) due to severe regression after a varicella infection.
She is now 6 years and 4 months old. Her expressive
language is evaluated as equal to a 5-year-old child,
receptive language and nonverbal communication is equal
to her peer group. General knowledge is above her age
group. There is still presence of stereotyped behavior,
restrictive and repetitive interest and activity, and she is
still very anxious during social interaction. There is no
spontaneous behavior at all; every goal-oriented activity
needs to be prompted.
Her younger brother (MIG) first came to the
University Children’s Hospital 2 years ago, when he was
2 years old. Clinical observation confirmed speech and
language difficulties (absence of expressive language and
very poor receptive language), very poor nonverbal communication,
very poor gaze phenomena, not responsive
to his own name, very poor social skills and interaction,
many stereotyped behaviors, very poor play skills, very
poor general knowledge and frequent meltdowns. He was
also diagnosed as being autistic, according to the DSM-5
criteria for autism. Generally, his clinical manifestation of
autism was much more severe than in his sister. He was
treated in the same manner as his sister. He is now 4 years
and 9 months old. His expressive and receptive language
is evaluated as equal to a 3-year-old child, his nonverbal
communication and general knowledge are equal to his
peer group, there is still strong presence of stereotyped
behavior, restrictive and repetitive interest and activity, and
he is very anxious during social interaction. Meltdowns
are now rare.
Both siblings do not have significant dysmorphic
features. At the time of obtaining the genetic results of the
first two siblings, the mother was 6 months pregnant with
twins. The genetic evaluation for this duplication was not
available at this time, so the parents decided to go forward
with the pregnancy. The twin boys were evaluated soon
after delivery, with extensive genetic counseling of the
parents. The same genetic duplication was also confirmed
in both of the twins. At the moment, the twins are 26
months old. They have been evaluated to have a delay of 6
months in expressive language, but all other developmental
milestones have been met. The same duplication was also found in the father, who has high intellectual capacities
and without any psychiatric disorders. The family tree of
this family is presented in Figure 1.
Genetic analysis was performed by the team of Research
Centre for Genetic Engineering and Biotechnology
“Georgi D. Efremov” (ICBIB) at the Macedonian
Academy
of Sciences and Arts, Skopje, RNM. The procedure
was as follows: 1) isolation of DNA with phenolchlorophorm
and ethanol precipitation; 2) aCGH with Sure
Print G3 CGH 4×180 kb, oligo microarray kit; Agilent
Technologies, Santa Clara, CA, USA, mean distance between
probes was 13 kb; the analysis of the results used
Agilent Technologies genomic Workbench software and
database for genomic variants, University of Santa Cruz
(UCSC) genome browser, ClinVar database (https://www.
clinical genome.org). The obtained result was: ISCN arr
cgh 16p.13.11-p12.3 (15,399,818-18,069,668) × 3. The
referent sequence: human genome builds 36 (hg 18).
Interpretation. The aCGH of DNA material obtained
for the patients showed chromosomic micro duplication of
the short arm of the chromosome in the 16p13.11-p12.3
region. The minimal size of the duplication is 2.67 Mb. The
deleted region encompasses 11 genes: MVP17L, C16orf45,
KIAA0430, NDEI, MYH11, C16orf63, ABCC1, ABCC6,
NOMO3, LOC339047, XYLTI.
The database information confirms this duplication
to be related to neurodevelopmental disorders, cognitive
delay, some neuropsychiatric disorders, but also in people
with a “normal phenotype.” Results obtained for our patients
confirmed genetic etiology of neurodevelopmental
delay as well as autistic behavior. The same mutation
was found in the twins: I = 16p.13.11-p12.3 (15492317_
18162167) ×4 with the minimal size of the duplication
of 2.67 Mb; II = 16p.13.11-p12.3 (15492317_18162167)
×4 with the same size of the duplication of 2.67 Mb.
Fortunately, their follow-up showed practically typical
development.
|
|
|
|
 |
Number 27
VOL. 27 (2), 2024 |
Number 27
VOL. 27 (1), 2024 |
Number 26
Number 26 VOL. 26(2), 2023 All in one |
Number 26
VOL. 26(2), 2023 |
Number 26
VOL. 26, 2023 Supplement |
Number 26
VOL. 26(1), 2023 |
Number 25
VOL. 25(2), 2022 |
Number 25
VOL. 25 (1), 2022 |
Number 24
VOL. 24(2), 2021 |
Number 24
VOL. 24(1), 2021 |
Number 23
VOL. 23(2), 2020 |
Number 22
VOL. 22(2), 2019 |
Number 22
VOL. 22(1), 2019 |
Number 22
VOL. 22, 2019 Supplement |
Number 21
VOL. 21(2), 2018 |
Number 21
VOL. 21 (1), 2018 |
Number 21
VOL. 21, 2018 Supplement |
Number 20
VOL. 20 (2), 2017 |
Number 20
VOL. 20 (1), 2017 |
Number 19
VOL. 19 (2), 2016 |
Number 19
VOL. 19 (1), 2016 |
Number 18
VOL. 18 (2), 2015 |
Number 18
VOL. 18 (1), 2015 |
Number 17
VOL. 17 (2), 2014 |
Number 17
VOL. 17 (1), 2014 |
Number 16
VOL. 16 (2), 2013 |
Number 16
VOL. 16 (1), 2013 |
Number 15
VOL. 15 (2), 2012 |
Number 15
VOL. 15, 2012 Supplement |
Number 15
Vol. 15 (1), 2012 |
Number 14
14 - Vol. 14 (2), 2011 |
Number 14
The 9th Balkan Congress of Medical Genetics |
Number 14
14 - Vol. 14 (1), 2011 |
Number 13
Vol. 13 (2), 2010 |
Number 13
Vol.13 (1), 2010 |
Number 12
Vol.12 (2), 2009 |
Number 12
Vol.12 (1), 2009 |
Number 11
Vol.11 (2),2008 |
Number 11
Vol.11 (1),2008 |
Number 10
Vol.10 (2), 2007 |
Number 10
10 (1),2007 |
Number 9
1&2, 2006 |
Number 9
3&4, 2006 |
Number 8
1&2, 2005 |
Number 8
3&4, 2004 |
Number 7
1&2, 2004 |
Number 6
3&4, 2003 |
Number 6
1&2, 2003 |
Number 5
3&4, 2002 |
Number 5
1&2, 2002 |
Number 4
Vol.3 (4), 2000 |
Number 4
Vol.2 (4), 1999 |
Number 4
Vol.1 (4), 1998 |
Number 4
3&4, 2001 |
Number 4
1&2, 2001 |
Number 3
Vol.3 (3), 2000 |
Number 3
Vol.2 (3), 1999 |
Number 3
Vol.1 (3), 1998 |
Number 2
Vol.3(2), 2000 |
Number 2
Vol.1 (2), 1998 |
Number 2
Vol.2 (2), 1999 |
Number 1
Vol.3 (1), 2000 |
Number 1
Vol.2 (1), 1999 |
Number 1
Vol.1 (1), 1998 |
|
|
