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A novel mutation and novel features in Nijmegen breakage syndrome
  6. R VARON,
  7. A REIS**,
  8. D BESANA164,
  9. A GUALA,
  10. L TIEPOLO*
  1. *Biologia Generale e Genetica Medica, Università di Pavia, Italy
  2. †Dipartimento di Genetica e Biologia Molecolare, Università “La Sapienza”, Roma, Italy
  3. ‡Centro Genetica Evoluzionistica, CNR, Roma, Italy
  4. §Dipartimento di Biologia, Università “Roma Tre”, Roma, Italy
  5. ¶Institut fur Umangenetik, Umboldt Universitat, Berlin, Germany
  6. **Molecular Genetics and Gene Mapping Centre, Max-Delbrueck-Centre, Berlin, Germany
  7. 164Neuropsichiatria Infantile, Ospedale C Arrigo, Alessandria, Italy
  8. ‡Divisione di Pediatria Ospedale S Andrea, Vercelli, Italy
  1. Dr Maraschio, Via Forlanini 14, 27100 Pavia, Italy, Marasc{at}

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Editor—Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder, characterised by microcephaly, bird-like face, growth retardation, immunodeficiency, cytogenetic abnormalities, increased radiosensitivity, and high susceptibility to lymphoid malignancy. The NBS1 gene, mapped on chromosome 8q211 and recently cloned,2 3codes for nibrin, a member of the hMre11/hRAD50 protein complex, involved in DNA double strand break repair. The NBS Registry in Nijmegen includes 55 patients. The majority of them are of eastern European origin and share a common haplotype, suggesting a founder effect, and a mutation consisting of a truncating 5 bp deletion in exon 6, 657-661 del ACAAA.4 Five further mutations have been found in six patients with different haplotypes and of various ethnic origins.

We found a new mutation of the NBS1 gene in a 2 year old girl from Morocco. The patient, a girl born at term in August 1997 (fig 1), is the third child of apparently non-consanguineous parents; the two brothers, aged 12 and 6 years, are healthy. The pregnancy was uneventful until the 33rd week, when growth retardation, dilatation of the cerebral ventricles, and agenesis of the corpus callosum was diagnosed by ultrasound examination.

Figure 1

(A) The patient at 18 months. (B) The right hand with preaxial polydactyly.

Birth weight was 2520 g (3rd centile), length 46 cm (<3rd centile), and head circumference 28.5 cm (<3rd centile). Physical examination showed a “bird-like” face with strabismus, downward slanting palpebral fissures, large and low set dysmorphic ears, and a high palate. The hands showed right preaxial polydactyly and bilateral clinodactyly of the fifth finger with a short middle phalanx and single flexion crease. The feet showed bilateral cutaneous syndactyly 4-5. Severe gastro-oesophageal reflux was also present. Normal findings were obtained on ultrasound examination of the heart and abdominal structures including the ovaries. Agenesis …

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