Short reportPrenatal diagnosis of mosaicism for 11q terminal deletion
Introduction
Jacobsen syndrome, or distal deletion of the long arm of chromosome 11 (OMIM#147791), is a rare but clinically well known entity [9], [11], [20] and has an incidence of approximately 1 in 100 000 births. Patients usually have visible deletions based on karyotype analysis: the breakpoint arises typically in 11q23.3 sub-band but can be located in 11q24 or 11q25 with deletions extending to the telomere [15]. Most frequently (85%), this deletion appears de novo. Other cases are the result of malsegregation from balanced parental rearrangements; in some patients Jacobsen syndrome is associated with a de novo chromosomal event as ring chromosome 11 [6]. There is a broad clinical spectrum of Jacobsen syndrome. Clinical manifestations can include developmental delay, psychomotor retardation, short stature, craniofacial features (trigonocephaly, hypertelorism, broad and flat nasal bridge, carp-shaped mouth with thin upper lip, low-set malformed ears), congenital heart defects (hypoplastic left heart syndrome, membranous ventricular septal defect, aortic arch defects), genitourinary anomalies, pyloric stenosis, ocular malformations (ptosis, colobomas, cataracts, glaucoma, strabismus, telecanthus), limb anomalies (talipes equinovarus, clino- or camptodactyly, syndactyly), recurrent infectious episodes and thrombocytopenia or pancytopenia. Hematological features in PTS include thrombocytopenia with or without pancytopenia and platelet abnormalities [2], [7]. Favier et al. [8] noted clinical, hematological and cytogenetic similarities between Jacobsen syndrome and PTS. They concluded that there is clearly a clinical overlap between these two syndromes, which are both associated with 11q terminal deletion. In the PTS, hemizygous deletion of the monoallelic expressed FLI1 gene contributes to the hematopoietic defects. The majority of Jacobsen syndrome affected cases were reported in infancy and childhood, however 14 affected fetuses were described with different pregnancy outcomes [4]. Only two cases of prenatally diagnosed 11q terminal deletion mosaicism are described in the literature [3], [16]. In the present study, we report on a fetus with 11q terminal deletion mosaicism. The fetus presented with minor clinical features of Jacobsen syndrome after second trimester ultrasound examination but very suggestive hematological anomalies on cord blood.
Section snippets
Case report
A 37-year-old primigravid woman underwent amniocentesis at 21 weeks' gestation because of a serum screening test positive for Down syndrome (1/78 for a normal test at 1/250) without ultrasound anomalies at the first examination. At 14.4 weeks' gestation, the maternal blood screening test showed a serum alpha-fetoprotein level of 0.66 multiples of the median (MoM) and a serum β-human chorionic gonadotrophin level of 1.52 MoM. Amniocentesis was performed at 21 weeks' gestation for foetal karyotype
Results
The first amniocentesis allowed the characterization of a mosaic karyotype: 46,XY[16]/46,XY,del(11)(q23)[3]. A second amniocentesis was realized at 24 week's gestation: 7 out of 36 colonies showed the same 11q terminal deletion extending from the 11q23 sub-band to the telomere (Fig. 1A). Fluorescence in situ hybridization (FISH) studies with 11q subtelomeric probe (Fig. 1B) but also with a probe specific for the FLI1 gene (RP11-138K22; Fig. 1C) confirmed the mosaic deletion with a mosaicism rate
Discussion
Jacobsen syndrome is a well known contiguous gene syndrome resulting from 11q23.3-qter deletion. The human reference genome at the National Center for Biotechnology Information (NCBI build 36.2) (http://www.ncbi.nlm.nih.gov) reports the localization of a total of 248 genes in this chromosomal region. Clinical signs of Jacobsen syndrome can include Paris–Trousseau type of thrombocytopenia if the deletion extends to 11q23. If the diagnosis of Jacobsen syndrome is easily established in infancy and
References (20)
- et al.
A new congenital dysmegakaryopoietic thrombocytopenia (Paris–Trousseau) associated with giant platelet alpha-granules and chromosome 11 deletion at 11q23
Blood
(1995) - et al.
Prenatal diagnosis of a large de novo terminal deletion of chromosome 11q
Prenat. Diagn
(2006) - et al.
European collaborative study on prenatal diagnosis: mosaicism, pseudomosaicism and single abnormal cells in amniotic fluid cell cultures
Prenat. Diagn
(1984) - et al.
Prenatal diagnosis of the distal 11q deletion and review of the literature
Prenat. Diagn
(2004) - et al.
Prenatal diagnosis of de novo distal 11q deletion associated with sonographic findings of unilateral duplex renal system, pyelectasis and orofacial clefts
Prenat. Diagn
(2001) - et al.
Chromosome 11, monosomy 11q
- et al.
A novel genetic thrombocytopenia (Paris–Trousseau) associated with platelet inclusions, dysmegakaryopoiesis and chromosome deletion AT 11q23
C R, Acad. Sci. III
(1993) - et al.
Paris–Trousseau syndrome: clinical, hematological, molecular data of ten new cases
Thromb. Haemost
(2003) - et al.
Distal 11q monosomy. The typical 11q monosomy syndrome is due to deletion of subband 11q24.1
Clin. Genet.
(1986) - et al.
The 11q terminal deletion disorder: a prospective study of 110 cases
Am. J. Med. Genet. A
(2004)
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