Subtelomeric monosomy 11q and trisomy 16q in siblings and an unrelated child: Molecular characterization of two der(11)t(11;16)

Abstract

We report here three children with a der(11)t(11;16), two sibs (patients 1 and 2) having inherited a recombinant chromosome from a maternal t(11;16)(q24.3;q23.2) and a third unrelated child with a de novo der(11)t(11;16)(q25;q22.1), leading to partial monosomy 11q and trisomy 16q. Fluorescent in situ hybridization (FISH) using bacterial artificial chromosome (BAC) clones and array-CGH were performed to determine the breakpoints involved in the familial and the de novo rearrangements. The partial 11 monosomy extended from 11q24.3 to 11qter and measured 6.17-6.21 Mb in Patients 1 and 2 while the size of the partial 11q25->qter monosomy was estimated at 1.97-2.11 Mb for Patient 3. The partial 16 trisomy extended from 16q23.2 to 16qter and measured 8.93-8.95 Mb in Patients 1 and 2 while the size of the partial 16q22.1->qter trisomy was 20.82 Mb for Patient 3. Intraventricular hemorrhage and transitional thrombocytopenia were found in both sibs but not in the third patient. The FLI1 gene, which is the most relevant gene for thrombocytopenia in Jacobsen syndrome, was neither deleted in family A nor in Patient 3. We suggest that a positional effect could affect the FLI1 expression for these two sibs. Deafness of our three patients confirmed the association of this anomaly to 11q monosomy and tended to confirm the hypothetic role of DFNB20 in Jacobsen syndrome hearing loss. Both sibs shared most of the features commonly observed in Jacobsen syndrome, but not the third patient. This confirmed that terminal 11q trisomy spanning 1 to 1.97-2.11 Mb is not associated with a typical Jacobsen syndrome.

SNP array and phenotype correlation shows that FLI1 deletion per se is not responsible for thrombocytopenia development in Jacobsen syndrome

“…Moreover, we are unaware of any reports of a male with FLI1 haploinsufficiency and normal platelet function and count. Of 12 patients (six males) who underwent detailed array-based deletion analysis, only two girls (including the present patient 1) presented with FLI1 deletion without thrombocytopenia [Bernaciak et al, 2008;Tyson et al, 2008;Manolakos et al, 2009;Ji et al, 2010;Basinko et al, 2011;Takahashi et al, 2011]. Similarly, a general male predominance for thrombocytopenia has been described in patients <2 years of age [Donato et al, 2009].…”

A rare description of pure partial trisomy of 16q12.2q24.3 and review of the literature

“…For each segment, reported phenotypes are counted using the + symbol. References for cases in the table: q11!qter: (Eggermann et al, 1998;Hahm et al, 1987;Nevin et al, 1983;Ridler & McKeown, 1979); q12!qter: (Chen et al, 2003;Paladini et al, 1999); q13!qter: (Buckton & Barr, 1981;Davison & Beesley, 1984;Dowman et al, 1989;Hatanaka et al, 1984;Luberda-Zapa snik et al, 1995); q21!qter: (Balestrazzi et al, 1979;Calva et al, 1984;de Carvalho et al, 2010;Garau et al, 1980;Lessick et al, 1989;Maher et al, 1991;Mishra et al, 2018;Yue et al, 2019); q22!qter: (Basinko et al, 2011;Houlston et al, 1994;Nyhan et al, 1989;…”

“…For each segment, reported phenotypes are counted using the + symbol. References for cases in the table: q11 → qter: (Eggermann et al, 1998; Hahm et al, 1987; Nevin et al, 1983; Ridler & McKeown, 1979); q12 → qter: (Chen et al, 2003; Paladini et al, 1999); q13 → qter: (Buckton & Barr, 1981; Davison & Beesley, 1984; Dowman et al, 1989; Hatanaka et al, 1984; Luberda‐Zapaśnik et al, 1995); q21 → qter: (Balestrazzi et al, 1979; Calva et al, 1984; de Carvalho et al, 2010; Garau et al, 1980; Lessick et al, 1989; Maher et al, 1991; Mishra et al, 2018; Yue et al, 2019); q22 → qter: (Basinko et al, 2011; Houlston et al, 1994; Nyhan et al, 1989; Rethoré et al, 1982; Sousa et al, 2004; Tsien et al, 2005); q23 → qter: (Basinko et al, 2011; Maher et al, 1991; Papadopoulou et al, 2017; Savary et al, 1991); q24 → qter: (Baker et al, 2002; Brisset et al, 2002; Ferrero et al, 2006; Giardino et al, 2001; Maher et al, 1991; Zahn et al, 2005; Zhou et al, 2013); Unknown: (Eriksson et al, 1971; Ferguson Jr. & Hicks, 1987; Francke, 1972). These publications did not utilize modern chromosome analysis techniques; however, the phenotypic description is most consistent with involvement of large segment of 16q; for reference (Francke, 1972), the relevant case is #10.…”

Ion imprinted beads embedded cryogels for in vitro removal of iron from β‐thalassemic human plasma

“…Moreover, we are unaware of any reports of a male with FLI1 haploinsufficiency and normal platelet function and count. Of 12 patients (six males) who underwent detailed array‐based deletion analysis, only two girls (including the present patient 1) presented with FLI1 deletion without thrombocytopenia [Bernaciak et al, 2008; Tyson et al, 2008; Manolakos et al, 2009; Ji et al, 2010; Basinko et al, 2011; Takahashi et al, 2011]. Similarly, a general male predominance for thrombocytopenia has been described in patients <2 years of age [Donato et al, 2009].…”