s 363 Brazil. The use of the array CGH (aCGH) has aided significantly the genetic diagnosis in recent years. In our laboratory aCGH combined with conventional karyotyping allowed an improvement of 20% to 30% in the diagnostic rate of patients with intellectual disabillity, dysmorphisms, autism and developmental delay. We used the Affymetrix chip Cytoscan HD and 750 K Cytoscan arrays (Santa Clara, CA) and analysis through the respective software system and for conventional karyotype (G Banding). We selected 2 cases to report: Case 1: Two siblings with distinct developmental disturbance phenotypes. Sibling one is a 7-year-old female with severe developmental delay phenotype, microcephaly and consanguineous parents. She presented an interstitial deletion of 12,1 Mb on chromosome 5, arr [hg19] 5p14.3p15.31 (6,801,589-18,992,827) 1, featuring the Cri-du-chat syndrome. Her brother, a 12-year-old male with mild intellectual disability (ID) a duplication of the exact same size and region that was deleted in the sister was found arr [hg19] 5p14.3-p15.31 (6,801,589-18,992,827) 3. Parental aCGH was normal. However, conventional karyotype of the father revealed 2 reciprocal translocation between chromosomes 1 and 2, 5 and 7: (46, XY, t(1, 2) (q44;w p23pter) t(5; 7)(p14.3-p15.31; p22). Case 2: A 16-year-old female with consanguineous parents and normal conventional karyotyping. She presents significant developmental delay, dyslalia, severe ID, autistic traits, irritability, hyperactivity and autoagression, without obvious dysmorphias and with normal: MRI, electroencephalogram and CT scan results. Microarray analysis revealed a homozygous microdeletion of 197 Kbp on chromosome 8:arr [hg19] 8p22 (15,451,748-15,649,733) 1, spanning almost the entire TUSC3 gene, except promoter and first exon (601385*).This is the seventh family with a reported TUSC3 mutation with mostly non syndromic ID and the second with the same deletion (Khan et al, 2011). Three of the families reported in the literature carried a deletion which encompassed only the TUSC3 promoter region and the first exon, 2 families presented distinct point mutations and 1 an intragenic duplication. All 7 families presented homozygous mutations, only 1 was not consanguineous however they were from the same village. Conclusion: These cases illustrate the importance of integrating conventional karyotyping techniques and microarray in genetic diagnosis. Both cases were referred for genetic counselling and family research. Unusual ROS1 Translocation Pattern in a 61 Year-old Woman with Metastatic Adenocarcinoma of Lung Hui Chen , Rajyalakshmi Luthra , Neda Kalhor , John Heymach , Ronald Abraham , Meenakshi Mehrotra , Bal Mukund Mishra , Keyur P. Patel , Rajesh R. Singh , Xinyan Lu b Department of Pathology, MD Anderson Cancer Center, Houston, TX, USA; Department of Hematopathology, MD Anderson Cancer Center, Houston, TX, USA; Department of Thoracic/Head N b Georgia Cancer Specialists and Northside Hospital Cancer Institute, Atlanta, GA, USA Recent studies show that Calreticulin (CALR) somatic mutations provide a diagnostic marker in JAK2/MPL wild type essential thrombocythemia (ET) and primary myelofibrosis (PMF) with a mutation frequency of 67% to 71% and 56% to 88%, respectively (Tefferi A and Pardanani A, Nat Rev Clin Oncol, 2014). In general, CALR mutations are not seen in Polycythemia Vera (PV), post-PV myelofibrosis or JAK2 V617F or MPL mutated ET or PMF. Studies showed that CALR mutations may also provide prognostic information and therefore is a promising molecular marker for diagnosis and prognosis for patients with myeloproliferative neoplasm (MPN). The exact mechanism by which CALR mutations produce the myeloproliferative disease phenotype is unknown, but multiple studies have shown that CALR mutations disrupt the C-terminal endoplasmic reticulum -retention sequence (KDEL), generate a novel C-terminus, and activate the STAT5 pathway. A 40-year-old female with persistent moderate thrombocytosis was referred for evaluation. Workup was negative for pseudo-thrombocytosis. She was noted to have mild iron deficiency. Reactive thrombocytosis and essential thrombocytosis were considered in the differential diagnosis. She was referred for clinical testing of CALR mutation analysis after she was found negative for JAK2. Mutation screening of CALR Exon 09 by PCR based Sanger sequencing revealed a novel mutation c.1191_1199del (p.E398_D400del) in this patient with African American ethnicity. Mutation status in CALR will aid the diagnosis of ET and PMF patients and risk stratification.
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Sep 26, 2016
Elin Yulinah Sukandar + 3
Open Access
