Güven TOKSOY, Benno RÖTHLİSBERGER, Bilge TURKOVER, Ceyhan SAYAR, Andreas R. HUBER4, Peter MİNY

Kromozom 1, 2, 4, 8, 14 ve 16’yı Içeren Kompleks Kromozom Anomalisinin Yol Açtığı Inserstisyal 4q Delesyonu

İki ya da daha fazla kromozom kırıklarının yol açtığı, kompleks kromozomal yeniden düzenlenmeleri (KKY) oldukça nadir gözlenmektedir. KKY lerin kesin olarak aydınlatılması moleküler tekniklerle dahi zorluklar içermektedir. Bu anomalilerin sitogenetik ve moleküler detaylarının açıklığa kavuşturulmasında MLPA, dizin teknolojileri (CGH, BAC, oligo, SNP, vd.) etkili olarak kullanılmaktadır. Bu çalışmada makrosefali, öne çıkık belirgin alın, epikantus, pitoz, mikrognati, düşük kulaklar kısa boyun, pectus ekskavatum, içe dönük sağ ayak, kriptoorşidi, hipotoni ve nörogelişimsel gerilik bulguları olan multipl konjenital anomalili olguda yapılan kromozom analizinde kromozom 1, 2, 4, 8, 14 ve 16 nın katıldığı KKY saptanan olgu sunuldu. Sitogenetik çalışma sonrası anormal karyotip (46,XY,der(1),der(2),der(4),t(8;14),der(16)) olarak saptandı. Ticari problarla metafaz FISH çalışması karyotip ish t(1:16),ins(4;2),t(8;14) detaylandırıldı. 500-550 bant düzeyinde yapılan kromozom analizinde görünüşte dengeli kromozom anomalisi ve klinik bulguların açıklanamaması nedeni ile yapılan dizin çalışmasında (array-CGH:NimbleGen), kromozom 4q(del(4)(q21.23q23) bölgesini kapsayan 14.7 MBb büyüklüğünde yaklaşık 50 genin bulunduğu büyük delesyon gösterildi.

Interstitial Deletion 4q due to a Complex Rearrangement Involving Chromosomes 1, 2, 4, 8, 14 and 16

Complex chromosome rearrangements (CCR’s) involving multiple breaks intwo or more chromosomes are rare. The precise characterization of a CCR isdifficult and may be inaccurate even by using molecular cytogenetictechniques. Various new molecular techniques such as MLPA, arraytechniques (CGH, BAC, oligo, SNP, etc.) have proved to be powerful tools forthe characterization of CCR’s. We present here a patient with a de novo CCRinvolving chromosomes 1, 2, 4, 8, 14, 16. He was investigated cytogeneticallybecause of multiple congenital anomalies such as macrocephaly with aprominent forehead, epicanthus, ptosis, micrognathia, low set ears, shortneck, pectus excavatum, adducted right foot, cryptorchidism, hypotonia andneurodevelopmental delay. Cytogenetic analysis revealed an abnormalkaryotype (46,XY,der(1),der(2),der(4),t(8;14),der(16)), while the parents had anormal chromosome count. After FISH investigations using differentcommercially available probes the karyotype was interpreted as isht(1:16),ins(4;2),t(8;14). The rearrangements were apparently balanced at a500-550 band level and revealed no obvious explanation for the phenotype ofthe index patient. Therefore, an array-CGH analysis (NimbleGen) was initiatedand a 14,7 Mb gross deletion was found in chromosome 4q(del(4)(q21.23q23))including approximately 50 genes.

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