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Mutations in MCOLN1 have been found to cause mucolipidosis type IV (MLIV; MIM 252650), a rare autosomal recessive lysosomal storage disorder found primarily in the Ashkenazi Jewish population. As a part of the successful cloning of MCOLN1, we constructed a 1.4-Mb physical map containing 14 BACs and 4 cosmids that encompasses the region surrounding MCOLN1 on human chromosome 19p13.3-p13.2--a region to which linkage or association has been reported for multiple diseases. Here we detail the precise physical mapping of 28 expressed sequence tags that represent unique UniGene clusters, of which 15 are known genes. We present a detailed transcript map of the MCOLN1 gene region that includes the genes KIAA0521, neuropathy target esterase ( NTE ), a novel zinc finger gene, and two novel transcripts in addition to MCOLN1. We also report the identification of eight new polymorphic markers between D19S406 and D19S912, which allowed us to pinpoint the location of MCOLN1 by haplotype analysis and which will facilitate future fine-mapping in this region. Additionally, we briefly describe the correlation between the observed haplotypes and the mutations found in MCOLN1. The complete 14-marker haplotypes of non-Jewish disease chromosomes, which are crucial for the genetic diagnosis of MLIV in the non-Jewish population, are presented here for the first time.

Mutations in MCOLN1have been found to cause mucolipidosis type IV (MLIV; MIM 252650), a rare autosomal recessive lysosomal storage disorder found primarily in the Ashkenazi Jewish population. As a part of the successful cloning of MCOLN1,we constructed a 1.4-Mb physical map containing 14 BACs and 4 cosmids that encompasses the region surrounding MCOLN1on human chromosome 19p13.3–p13.2—a region to which linkage or association has been reported for multiple diseases. Here we detail the precise physical mapping of 28 expressed sequence tags that represent unique UniGene clusters, of which 15 are known genes. We present a detailed transcript map of the MCOLN1gene region that includes the genes KIAA0521, neuropathy target esterase (NTE), a novel zinc finger gene, and two novel transcripts in addition to MCOLN1.We also report the identification of eight new polymorphic markers between D19S406and D19S912,which allowed us to pinpoint the location of MCOLN1by haplotype analysis and which will facilitate future fine-mapping in this region. Additionally, we briefly describe the correlation between the observed haplotypes and the mutations found in MCOLN1.The complete 14-marker haplotypes of non-Jewish disease chromosomes, which are crucial for the genetic diagnosis of MLIV in the non-Jewish population, are presented here for the first time.

The purpose of this study was to identify those critical factors that genetic nurse experts perceived could influence parental decision-making to seek or to reject presymptomatic testing of their children at risk for treatable adult-onset genetic disorders (neurofibromatosis 2, familial adenomatous polyposis, and von Hippel Lindeau disorder). Perceptions of ISONG genetic nurse specialists were surveyed through a modified Delphi technique and four major themes emerged: personal experience with severity of genetic disorder, receiving accurate information from credible sources, availability of quality treatment, and risk perception. Currently, there is a paucity of extant research that identifies critical factors influencing parental decision-making about this relatively new testing alternative for children. Thus, these experts are an important source of valuable information needed to identify such factors. Findings may be useful to design a qualitative study with parents to investigate this issue.