Confirmation of linkage of Hypokalemic periodic paralysis to chromosome 1q31-32: Further evidence supporting CACNL1A3 as a candidate gene
- Duke Univ. Medical Center, Durham, NC (United States); and others
Hypokalemic periodic paralysis (HOKPP; MIM 170400) is one entity of a series of periodic paralyses characterized by episodic bouts of weakness with onset in the second to third decades. The hypokalemic form is defined by decreased serum potassium during a paralytic attack. HOKPP can occur in both familial and sporadic forms; the familal form is autosomal dominant with reduced penetrance in female gene carriers. Recently, Fontaine et al. have localized HOKPP to 1q31-32 in three multigenerational HOKPP families. The region of sub-localization includes the CACNL1A3 gene, making it a potential candidate for the genetic defect in HOKPP. We have ascertained and sampled 2 large multigenerational HOKPP pedigrees (N = 55 individuals with DNA) for linkage analysis. The families were initially screened for linkage with over 150 marker loci located throughout the genome. Analysis of the chromosome 1 markers D1S412, D1S413 and F13B gave significant evidence for linkage. The peak two-point lod score realized was Z = 4.34 at theta = 0.0 (D1S413). A sex-dependent penetrance of 80% was assumed, although varying the penetrance did not significantly alter the results. There was no evidence for heterogeneity. Multipoint analysis of the data defined the region between D1S238 and D1S245 (which contains the CACNL1A3 gene) as the most likely region (> 1000 odds) for the location of the HOKPP gene. There were no obligate recombinants among males or affected females for the CACNL1A3 (Z = 3.19, theta = 0.0), although several potential non-penetrant females were identified. These studies confirm linkage of HOPKK to chromosome 1 in an independent data set, lend further support of CACNL1A3 as a potential candidate gene, and give evidence for homogeneity in this disease.
- OSTI ID:
- 134060
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0796
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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