Partial DiGeorge syndrome in two patients with a 10p rearrangement

Abstract

We describe 2 patients with a partial DiGeorge syndrome (facial dysmorphism, hypoparathyroidism, renal agenesis, mental retardation) and a rearrangement of chromosome 10p. The first patient carries a complex chromosomal rearrangement, with a reciprocal insertional translocation between the short arm of chromosome 10 and the long arm of chromosome 8, with karyotype 46, XY ins(8;10) (8pter 8q13::10p15-->10p14::8q24.1-->8qter) ins(10:8) (10pter--> 10p15::8q24.1-->8q13::10p14-->10qter). The karyotype of the second patient shows a terminal deletion of the short arm of chromosome 10. In both patients, the breakpoints on chromosome 10p reside outside the previously determined DiGeorge critical region II (DGCRII). This is in agreement with previous reports of patients with a terminal deletion of 10p with breakpoints distal to the DGCRII and renal malformations/hypoparathyroidism, and thus adds to evidence that these features may be caused by haploinsufficiency of one or more genes distal to the DGCRII.

Hypoparathyroidism‐retardation‐dysmorphism syndrome in a girl: A new variant not caused by a TBCE mutation—clinical report and review

“…In the differential diagnosis of our patient, we excluded other syndromes with congenital hypoPTH, such as deletion 22q11 syndrome (FISH 22q11.2 showed no deletion), a familial form of hypoPTH (PTH levels in both parents were normal), and 10p deletion syndrome (excluded by FISH) [Greenberg et al, 1986;Van Esch et al, 1999;Verri et al, 2004]. Rett syndrome could also be excluded Cohen et al [1996] describing an adult with congenital hypoPTH, dysmorphic features and MR, with a normal height and no microcephaly, no cardiovascular and immunological problems, and normal hands and feet.…”

Characterization of GATA3 Mutations in the Hypoparathyroidism, Deafness, and Renal Dysplasia (HDR) Syndrome

“…Thus, GATA1 mutations lead to dyserythropoietic anemia, thrombocytopenia (14), and the megakaryoblastic leukemia of Down's syndrome (15); GATA3 haploinsuf-ficiency is associated with the hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome (16); and GATA4 hemizygosity has been observed in some patients with congenital heart disease (17). More than 90% of HDR syndrome patients have hypoparathyroidism and deafness, and more than 80% have renal tract abnormalities (16,18,19). The hypoparathyroidism is characterized by symptomatic or asymptomatic hypocalcemia with undetectable or inappropriately normal serum concentrations of parathyroid hormone (PTH), and normal brisk increases in plasma cAMP in response to PTH infusion, which indicates normal sensitivity of the PTH receptor (18).…”

Interstitial deletion of the short arm of chromosome 10 del(10)(p11.2p12.32) in a patient with congenital heart disease, minor dysmorphism, and mental retardation

“…This deletion was first reported by Elliott et al [1970], however the association with DGS anomalies was not described until 1984 [Herve' et al, 1984]. Deletion of 10p14 and mutations in GATA3 are associated with the hypoparathyroidism, sensorineural deafness, and renal defects (HDR syndrome) [Hasegawa et al, 1997;Van Esch et al, 1999;Lichtner et al, 2000;Van Esch et al, 2000], whereas deletion of a more proximal region of the chromosome 10 short arm (10p13-14) is associated with cardiac and T-cell abnormalities; the only known gene in the 300Kb critical region is BRUNOL3, which is expressed strongly in the human thymus during different stages of development [Lichtner et al, 2002].…”

“…DGS1/VCFS1 occurs due to interstitial deletion of chromosome 22 in the proximal region of the long arm (del(22)(q11.21q11.21) [Scambler, 2000]. The features common to these 10p deletion cases and DGS1/VCFS1 include CHD, T-cell deficiency, hypoparathyroidism, hypocalcemia, facial anomalies, developmental and growth retardation, hearing loss, and genitourinary anomalies [Schuffenhauer et al, 1995;Daw et al, 1996;Van Esch et al, 1999]. CHDs occur in more than half of the patients with 10p deletions [Yatsenko et al, 2004].…”