1.Duplication 17p11.2 (Potocki-Lupski Syndrome) in a child with developmental delay
Salwati Shuib ; Nenny Noorina Saaid
The Malaysian Journal of Pathology 2017;39(1):77-81
Potocki-Lupski syndrome (PTLS), also known as duplication 17p11.2 syndrome, trisomy 17p11.2
or dup(17)(p11.2p11.2) syndrome, is a developmental disorder and a rare contiguous gene syndrome
affecting 1 in 20,000 live births. Among the key features of such patients are autism spectrum
disorder, learning disabilities, developmental delay, attention-deficit disorder, infantile hypotonia
and cardiovascular abnormalities. Previous studies using microarray identified variations in the size
and extent of the duplicated region of chromosome 17p11.2. However, there are a few genes which
are considered as candidates for PTLS which include RAI1, SREBF1, DRG2, LLGL1, SHMT1 and
ZFP179. In this report, we investigated a case of a 3-year-old girl who has developmental delay.
Her chromosome analysis showed a normal karyotype (46,XX). Analysis using array CGH (4X44
K, Agilent USA) identified an ~4.2 Mb de novo duplication in chromosome 17p11.2. The result was
confirmed by fluorescence in situ hybridization (FISH) using probes in the critical PTLS region.
This report demonstrates the importance of microarray and FISH in the diagnosis of PTLS.
2.Inherited t(9;22) as the cause of DiGeorge syndrome: a case report
Salwati Shuib ; Zarina Abdul Latif ; Nor Zarina Zainal ; Sharifah Noor Akmal ; Zubaidah Zakaria
The Malaysian Journal of Pathology 2009;31(2):133-136
DiGeorge syndrome is associated with microdeletion of chromosome 22q11.2. Most cases occur
sporadically although vertical transmission has been documented. We report a rare case of DiGeorge
syndrome in an 8-year-old girl. Blood sample of the patient was cultured and harvested following
standard procedure. All of the 20 cells analysed showed a karyotype of 45,XX,-22,t(9;22)(p23;q11.2).
Cytogenetic investigation done on the patient’s mother revealed that she was the carrier for the
translocation. Her karyotype was 46,XX,t(9;22)(p23;q11.2). Fluorescence in situ hybridisation
(FISH) analysis using TUPLE1 and N25 (Vysis, USA) probes showed deletion of the 22q11.2
region in the patient, confi rming the diagnosis of DiGeorge syndrome. FISH analysis showed no
deletion of the region in the mother.
3.A case of chronic myeloid leukaemia in blast transformation with leukemic ascites
Mohd Ridzuan Mohd Said ; Ernie Yap ; Wan Fariza Wan Jamaluddin ; Fadilah S Abdul Wahid ; Salwati Shuib
The Medical Journal of Malaysia 2016;71(2):85-87
Chronic Myeloid Leukaemia (CML) is a disease
characterised by a distinctive marker that is the Philadelphia
Chromosome and an ability to transform into blast phase,
which confers a poor prognosis. The median survival was
reported to be between three to six months in correlation to
blast phase. Extramedullary involvement with CML to sites
such as pleural, meningeal and bones have been reported.
We report a case of 41-year-old man who was diagnosed
with CML in blast phase and presented with ascites.
Ultrasound of abdomen showed coarse echotexture of liver
suggestive leukaemic infiltration to the liver. The liver profile
was severely deranged and associated with coagulopathy.
Flow cytometry analysis of the peritoneal fluid revealed
presence of myeloblasts consistent with CML in blast crisis
with leukaemic ascites. Bone marrow biopsy also confirmed
disease transformation. He received standard induction
chemotherapy for acute myeloid leukaemia with dose
modifications based on liver enzymes performance. Our
case highlights an unusual presentation of CML in blast
crisis with leukaemic ascites and the challenges in
managing cytotoxic treatments due to the liver infiltration.
Leukemia, Myeloid, Acute
4.Dismal outcome of therapy-related myeloid neoplasm associated with complex aberrant karyotypes and monosomal karyotype: a case report
Tang Yee-Loong’ Chia Wai-Kit ; Yap Ernie Cornelius Sze-Wai ; Julia Mohd Idris ; Leong Chooi-Fun ; Salwati Shuib ; Wong Chieh-Lee
The Malaysian Journal of Pathology 2016;38(3):315-319
Introduction: Individuals who are exposed to cytotoxic agents are at risk of developing therapyrelated
myeloid neoplasms (t-MN). Cytogenetic findings of a neoplasm play an important role in
stratifying patients into different risk groups and thus predict the response to treatment and overall
survival. Case report: A 59-year-old man was diagnosed with acute promyelocytic leukaemia.
Following this, he underwent all-trans retinoic acid (ATRA) based chemotherapy and achieved
remission. Four years later, the disease relapsed and he was given idarubicin, mitoxantrone and
ATRA followed by maintenance chemotherapy (ATRA, mercaptopurine and methotrexate). He
achieved a second remission for the next 11 years. During a follow-up later, his full blood picture
showed leucocytosis, anaemia and leucoerythroblastic picture. Bone marrow examination showed
hypercellular marrow with trilineage dysplasia, 3% blasts but no abnormal promyelocyte. Fluorescence
in-situ hybridisation (FISH) study of the PML/RARA gene was negative. Karyotyping result
revealed complex abnormalities and monosomal karyotype (MK). A diagnosis of therapy-related
myelodysplastic syndrome/myeloproliferative neoplasm with unfavourable karyotypes and MK was
made. The disease progressed rapidly and transformed into therapy-related acute myeloid leukaemia
in less than four months, complicated with severe pneumonia. Despite aggressive treatment with
antibiotics and chemotherapy, the patient succumbed to the illness two weeks after the diagnosis.
Discussion and Conclusion: Diagnosis of t-MN should be suspected in patients with a history of
receiving cytotoxic agents. Karyotyping analysis is crucial for risk stratification as MK in addition
to complex aberrant karyotypes predicts unfavourable outcome. Further studies are required to
address the optimal management for patients with t-MN.
5.Penjujukan Eksom Bagi Penyakit Jarang Jumpa, Mullerian Agenesis dan Agenesis Anotectal anomaly: Kajian Kes (Whole Exome Sequencing of a Rare Disease, Mullerian Agenesis and Anorectal Anomaly: A Case Report)
Siti Aishah Sulaiman ; Nor Azian Abdul Murad ; Yock Ping Chow ; Muhammad-Redha Abdullah-Zawawi ; Zam Zureena Mohd Rani ; Siti Nurmi Nasir ; Salwati Shuib ; Dayang Anita Abdul Aziz ; Hana Azhari ; Sharifah Azween Syed Omar ; Zarina Abdul Latiff ; Rahman Jamal
Malaysian Journal of Health Sciences 2024;22(No.2):18-38
Mullerian agenesis or Mayer-Rokitansky-Kuster-Hauser Syndrome (MRKH) Type-II is a
congenital defect in the Mullerian duct that results in the absence of a uterus in women. The
aetiology of this syndrome is unknown and has been considered a sporadic genetic disease.
MRKH, together with anorectal anomaly, is an extremely rare condition and has only been
reported in a few cases without any information on genetic analysis. This study investigated the mutational profile of a girl diagnosed with MRKH and anorectal anomalies with
rectovaginal fistula. The whole exome sequencing (WES) trio-genetic analysis of a 5-year-old
Malaysian girl diagnosed with MRKH (having anorectal anomaly with rectovaginal fistula)
was performed together with her normal parents, using the Ion AmpliSeq Exome RDY kit
(ThermoFisher Scientific, USA). Data were analysed using Torrent Suite v.5.0.4 and annotated
using ANNOVAR. Single nucleotide polymorphisms (SNPs) with an allele frequency >0.01
were excluded, and the remaining variants were filtered based on de novo mutations,
autosomal recessive, and autosomal recessive genetic traits. Related genes were analysed by
biological pathway analysis (g:Profiler) and protein-protein interaction (HIPPIE v.2.3,
STRING v.11.5, dan GeneMANIA). A total of 36 mutations were identified, and two of them,
the LHX5 (p.P358Q), inherited from the father, and CFTR (p.R1158X), inherited from the
mother. There were 28 de-novo mutations from 28 genes. All genes were involved in 27
biological processes that connected with 23 interactions, and are likely to cause MRKH
syndrome in this patient.
6.Comparison of Clinicopathological Parameters, and Treatment Responses in Younger and Older Chronic Myeloid Leukaemia Patients Treated with Imatinib
Ahmad Farhan Kamarudin ; Sivakumar Palaniappan ; Raja Zahratul Azma Raja Sabudin ; Salwati Shuib ; Siti Afiqah Muhamad Jamil ; Nor Rafeah Tumian
Malaysian Journal of Medicine and Health Sciences 2023;19(No.6):101-110
Introduction: Differences in baseline characteristics and response to treatment in different age groups of patients with chronic myeloid leukaemia (CML) in resource-limited countries have not been extensively studied. We aimed to determine the differences in clinicopathological parameters at diagnosis and response to imatinib in adult CML patients with younger (under 60 years; YCML) and older (60 years and older; OCML) age treated at our institution from March 2001 to March 2021. Methods: A retrospective analysis of consecutive adult CML patients receiving imatinib was performed. Clinicopathological parameters and treatment response were reviewed and analysed using
hospital medical records and electronic data reports. Results: The median age at diagnosis was 50 years. OCML patients (n=17) had significantly more comorbidities. The YCML group (n=50) generally had a palpable spleen >5cm from the costal margin, mild anaemia, hyperleukocytosis and thrombocytosis. A starting dose of 400 mg/day was observed in 84% of YCML and in 65% of OCML. Cumulative complete cytogenetic response was 50% in YCML versus 70.6% in OCML, p=0.158. OCML tended to have a higher percentage of major molecular response (MMR) (52.9%
versus 32%) and a shorter time to MMR, 22 months (range 5-70) versus 35 months (range 8-53). OCML experienced more haematological and non-haematological treatment-related adverse events after imatinib therapy. Conclusion: Although OCML patients had more comorbidities and treatment intolerances, overall long-term treatment response was comparable to YCML. In OCML, a more personalised approach to initial and subsequent dosing of imatinib may be considered.