The ATP-dependent DNA helicase Q4 (RECQL4) belongs to a family of conserved RECQ helicases that are felt to be important in maintaining chromosomal integrity (Kitao et al., 1998, Genomics: 54 (3): 443-452). Deletions in the RECQL4 gene located on chromosome 8 region q24.3 have been associated with Rothmund-Thomson syndrome (RTS, OMIM 268400), a condition characterized by poikiloderma, sparse hair, small stature, skeletal abnormalities, cataracts and an increased risk of malignancy. We present a patient with a molecularly confirmed diagnosis of RTS with two unique genetic alterations in RECQL4 (IVS16-2A>T and IVS2+27_51del25), who at the age of 7 months nearly succumbed to Pneumocystis carinii pneumonia. Evaluation of his immune system demonstrated a T- B+ NK- phenotype with agammaglobulinemia consistent with combined immunodeficiency (CID). Studies to evaluate for known genetic causes of CID were not revealing. The patient received an umbilical cord blood (UCB) transplant with complete immune reconstitution. This report represents the first description of a CID phenotype and UCB transplantation in a patient with RTS.

We report on a family ascertained through a 14-month-old girl with a terminal deletion of chromosome 8p23.1. Analysis of the karyotype of other relatives showed that the mother is the carrier of a balanced complex 4-break chromosome rearrangement, which she and her brother inherited from their father following recombination. This complex chromosome rearrangement (CCR) was confirmed by fluorescence in-situ hybridization (FISH) using libraries for chromosomes 1, 8, and 9, and telomeric probes for the long arm of chromosome 9. The karyotype of the maternal grandfather was 46,XY,t(1;8) (p31;q21.1),t(8;9) (p23.1;q34). The karyotype of his daughter is 46,XX,rec(8)t(1;8) (p31;q21.1)t(8;9)(p23.1;q34)pat. The karyotype of the proposita is 46,XX,rec(8)t(8;9) (p23.1;q34)mat, and that of her abnormal elder sister is 46,XX,t(1;8)(p31;q21.1)rec(8) t(8;9) (p23.1;q34)mat,der(9)t(8;9) (p23.1;q34) mat. Unbalanced segregation and/or recombination during maternal meiosis gave rise to the two abnormal sisters, one effectively with 8p trisomy and the other with monosomy for that same 8p segment. To our knowledge, this is the first case of a familial CCR giving rise to unbalanced recombination products.

We report on a 5-year-old boy with minor anomalies, growth retardation, and developmental delay carrying an extra chromatin material on the terminal band of the long arm of chromosome 6. To determine the origin of this extra material, whole chromosome fluorescence in situ hybridization (FISH) was used initially. Results showed fully painted 6qs, excluding the possibility of a derivative. However, maternal cytogenetic investigation suggested the presence of a possible half-cryptic balanced translocation that was further assessed using specific subtelomeric FISH probes of chromosome 6. Results showed that the 6q subtelomeric region was translocated on an A-group chromosome that was ultimately characterized, using FISH, as chromosome 2. This illustrates the use of specific subtelomeric regions and the limitations of whole chromosome FISH to identify the origin of a subtle chromosomal abnormality.

We report a familial deletion of (8q) detected in amniocytes of a fetus with a normal ultrasound and in the phenotypically normal mother, who has now had three pregnancy losses. Chromosome analysis of amniocytes and maternal peripheral blood cells showed an interstitial deletion of (8)(q24.13q24.22), which is distal to the region associated with Langer-Giedion syndrome (LGS) or trichorhinophalangeal (TRP) syndrome. This deletion was confirmed by fluorescence in situ hybridization with a c-myc cosmid clone and chromosome 8 painting library.