Ibis Menéndez

Q829X, a novel mutation in the gene encoding otoferlin (OTOF), is frequently found in Spanish patients with prelingual non-syndromic hearing loss

Inherited hearing impairment is a highly heterogeneous group of disorders with an overall incidence of about 1 in 2000 newborns.1 Among them, prelingual, severe hearing loss with no other associated clinical feature (non-syndromic) is by far the most frequent.1 It represents a serious handicap for speech acquisition, and therefore early detection is essential for the application of palliative treatment and special education. Hence genetic diagnosis and counselling are being increasingly demanded. Non-syndromic prelingual deafness is mainly inherited as an autosomal recessive trait. To date, 28 different loci for autosomal recessive non-syndromic hearing loss have been reported and 10 genes have been identified.2 Mutations in the gene encoding connexin-26 ( GJB2 , DFNB1 locus) are responsible for up to 50% of all cases of autosomal recessive deafness, with a frequent mutation (35delG) accounting for up to 86% of the GJB2 mutant alleles in several populations.3–10 Other mutations, 235delC and 167delT, account for the majority of GJB2 mutant alleles among the Japanese11 and Ashkenazi Jewish populations,12 respectively. However, little is known about the individual contribution of other genes and their mutations to the remaining uncharacterised cases. Two factors explain this lack of knowledge. First, most of the deafness genes identified so far are large, with many exons and no mutational hotspots, a problem that hampers routine molecular diagnosis. Second, the recent impressive progress in the investigation of genetic deafness has been the result of a research strategy based on the study of large pedigrees with many affected subjects.13 As a consequence, for most of the genes identified so far, genetic linkage has been reported only for a few families, and a small number of mutations have been published.14–23 In contrast, most of the families asking for a genetic diagnosis are small, with only …

Two independent RB1-inactivating mutations in peripheral blood DNA of a hereditary retinoblastoma patient.

We report the presence of a hemizygous inactivating germ‐line RB1 mutation (a recurrent g.78250C→T transition, resulting in a stop codon in exon 17) in peripheral blood DNA from a patient with hereditary bilateral retinoblastoma. Hemizygosity was established by sequencing that showed no traces of the wild‐type C nucleotide and by quantitative real‐time PCR, which showed loss of one copy of exon 17. Genotyping of the RB1 locus with several polymorphic markers delineated a maximal deletion region between g.76875 and g.99426, including exons 15–17 and a large piece (21 kb) of intron 17. The heterozygosity for the mutation found in skin fibroblasts proves that the intragenic RB1 deletion probably took place in the definitive hematopoietic lineage of the patient. The presence of a null Rb−/− genotype in the hematopoietic cell lineage suggests that the white blood cells of the proband could be useful in the investigation of the role of complementary RBI family proteins in the control of the cell cycle.