Single gene disorders

  • Yoni Sheynin
  • Published 2008 in Genomic Medicine

Abstract

Single gene disorders Human Genome Organisation (HUGO) International Limited 2009 008: Study of the gene causing congenital insensitivity to pain among Israeli-Beduins Yoni Sheynin, Zamir Shorer, Jacov Levy, Ruti Parvari Department of Virology and Developmental Genetics, Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva, Israel, Division of Pediatrics, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva, Israel Background: Congenital insensitivity to pain (CIP) syndrome is one of the rare hereditary sensory autonomic neuropathies. We characterized a Beduin family from the Negev, in which three individuals suffer from this disease. Aim: To identify the mutation which causes the disease. Methods: A SNP genotyping using the GeneChip mapping 250 K array was performed with samples from the three affected individuals and one unaffected parent in the family. Homozygosity mapping and sorting of genomic regions were performed with software specially programmed for this purpose. Several regions were selected upon their physical size and number of SNPs they contain. These regions were genotyped for all members of the family with microsatellite markers and linkage was found to one region. Sequencing of the genes in the interval was done to identify the mutation causing the disease. Results and Conclusions: We have mapped the locus to a 14.2 Mb region on chromosome 2q. Screening of candidate genes in this region identified a protein-damaging mutation in SCN9A gene, which encodes for the voltage-gated sodium channel Nav1.7. This mutation was not found in 130 healthy Beduins. 009: Novel CUL7 mutation in 49 Yakut patients with short stature syndrome Nadejda Maksimova, Kenju Hara, Akinori Miyashita, Irina Nikolaeva, Anna Nogovicina, Aitalina Sukhomyasova, Masatoyo Nishizawa, Osamu Onodera Yakut Scientific Centre, Siberian Department of Russian Academy of Medical Sciences, 677019 4, Sergelyakhskoye shosse, Yakutsk, Russia, Brain Research Institute, Niigata University, 951-8585 1-757 Asahi-machi-dori, Niigata, Japan, Republican Hospital National Medical Centre, 677019 4, Sergelyakhskoye shosse, Yakutsk, Russia Yakuts have a high frequency of some hereditary diseases, because they have experienced a serious bottleneck effect. Hereditary short stature syndrome is one of the major concerns in Yakuts. We have identified 49 patients with short stature syndrome in 43 Yakut families with preand post-natal non-progressive growth failure, facial dysmorphism and normal intelligence. The average of birth length was 42.0 cm ± 6.2 standard deviation score (SDS), and that of weight was 2.330 kg. A genome-wide linkage analysis for these families revealed linkage to region 6p21.1 with the highest multipoint LOD score of 24.6 at D6S282. We applied a homozygosity mapping approach and narrowed the causative gene to the same locus of the 3-M syndrome and the gloomy face syndrome (Huber et al. 2005). We found a novel homozygous 4582insT mutation in CUL7, which resulted in a frameshift and subsequent premature stop codon at 1,553 (Q1553X). The clinical presentations of 49 patients with short stature syndrome (from birth to 45 years) in Yakut were similar to those of 3M syndrome. However, they have a high frequency of neonatal respiratory distress (41.98%) and a low frequency of X-ray abnormalities. These findings may provide better understanding of the clinical diversity of short stature syndrome with the CUL7 mutation. 010: Molecular genetics of primary microcephaly

DOI: 10.1007/s11568-009-9115-4

Cite this paper

@article{Sheynin2008SingleGD, title={Single gene disorders}, author={Yoni Sheynin}, journal={Genomic Medicine}, year={2008}, volume={2}, pages={163-165} }