𝔖 Bobbio Scriptorium
✦   LIBER   ✦

Clinical variability and novel mutations in the NHEJ1 gene in patients with a Nijmegen breakage syndrome-like phenotype

✍ Scribed by Véronique Dutrannoy; Ilja Demuth; Ulrich Baumann; Detlev Schindler; Kateryna Konrat; Heidemarie Neitzel; Gabriele Gillessen-Kaesbach; Janina Radszewski; Susanne Rothe; Mario T. Schellenberger; Gudrun Nürnberg; Peter Nürnberg; Keng Wee Teik; Revathy Nallusamy; André Reis; Karl Sperling; Martin Digweed; Raymonda Varon

Publisher
John Wiley and Sons
Year
2010
Tongue
English
Weight
463 KB
Volume
31
Category
Article
ISSN
1059-7794

No coin nor oath required. For personal study only.

✦ Synopsis

We have previously shown that mutations in the genes encoding DNA Ligase IV (LIGIV) and RAD50, involved in DNA repair by nonhomologous-end joining (NHEJ) and homologous recombination, respectively, lead to clinical and cellular features similar to those of Nijmegen Breakage Syndrome (NBS). Very recently, a new member of the NHEJ repair pathway, NHEJ1, was discovered, and mutations in patients with features resembling NBS were described. Here we report on five patients from four families of different ethnic origin with the NBS-like phenotype. Sequence analysis of the NHEJ1 gene in a patient of Spanish and in a patient of Turkish origin identified homozygous, previously reported mutations, c.168C4G (p.Arg57Gly) and c.532C4T (p.Arg178Ter), respectively. Two novel, paternally inherited truncating mutations, c.495dupA (p.Asp166ArgfsTer20) and c.526C4T (p.Arg176Ter) and two novel, maternal genomic deletions of 1.9 and 6.9 kb of the NHEJ1 gene, were found in a compound heterozygous state in two siblings of German origin and in one Malaysian patient, respectively. Our findings confirm that patients with NBS-like phenotypes may have mutations in the NHEJ1 gene including multiexon deletions, and show that considerable clinical variability could be observed even within the same family.

📜 SIMILAR VOLUMES

A patient with mutations in DNA Ligase I
A patient with mutations in DNA Ligase IV: Clinical features and overlap with Nijmegen breakage syndrome
✍ Tawfeg I. Ben-Omran; Karen Cerosaletti; Patrick Concannon; Sheila Weitzman; Marj 📂 Article 📅 2005 🏛 John Wiley and Sons 🌐 English ⚖ 111 KB 👁 1 views

## Abstract The clinical phenotype of Ligase IV syndrome (LIG4 syndrome), an extremely rare autosomal recessive condition caused by mutations in the __LIG4__ gene, closely resembles that of Nijmegen breakage syndrome (NBS), and is characterized by microcephaly, characteristic facial features, growt

Genotype–phenotype relationships in tric
Genotype–phenotype relationships in trichothiodystrophy patients with novel splicing mutations in the XPD gene
✍ Elena Botta; Tiziana Nardo; Donata Orioli; Roberta Guglielmino; Roberta Ricotti; 📂 Article 📅 2008 🏛 John Wiley and Sons 🌐 English ⚖ 333 KB

Trichothiodystrophy (TTD) is a rare, autosomal recessive neurodevelopmental disorder most commonly caused by mutations in ERCC2 (XPD), a gene that encodes a subunit of the transcription/repair factor IIH (TFIIH). Here, we describe two TTD cases in which detailed biochemical and molecular investigati

Clinical and hematologic findings in Noo
Clinical and hematologic findings in Noonan syndrome patients with PTPN11 gene mutations
✍ Murat Derbent; Yekta Oncel; Kürşad Tokel; Birgül Varan; Ayşegül Haberal; A. Cana 📂 Article 📅 2010 🏛 John Wiley and Sons 🌐 English ⚖ 127 KB 👁 2 views

## Abstract Reports on Noonan syndrome (NS) have documented multiple types of coagulation defects and bleeding diathesis, and a wide range of clinical presentations. Early studies suggested that a large proportion of NS patients have coagulation defects, whereas more recent reports indicate low rat

Fifteen novel mutations in the JAGGED1 g
Fifteen novel mutations in the JAGGED1 gene of patients with Alagille syndrome
✍ Cécile Crosnier; Catherine Driancourt; Nicole Raynaud; Michelle Hadchouel; Michè 📂 Article 📅 2000 🏛 John Wiley and Sons 🌐 English ⚖ 23 KB 👁 2 views

Mutations in the human JAGGED1 gene cause Alagille syndrome, an autosomal dominant developmental disorder. The gene encodes a transmembrane protein which is a ligand of Notch receptors. We report 23 mutations in previously undescribed probands, including 15 novel mutations and 8 recurrent mutations.