ClinVar Genomic variation as it relates to human health

In 7 of 10 Greek families with juvenile hemochromatosis (HFE2A; 602390), Papanikolaou et al. (2004) identified a homozygous gly320-to-val (G320V) mutation in the HJV gene. Affected individuals shared the common Greek haplotype. This same mutation was found in 1 Canadian and 1 French family with juvenile hemochromatosis. In 1 Greek family, the G320V mutation was in compound heterozygous state with arg326 to ter (R326X; 608374.0002), and in 1 Canadian family, G320V was in compound heterozygous state with ile222 to asn (I222N; 608374.0003). In a white female diagnosed with hereditary hemochromatosis (HFE1; 235200) at the age of 30 years when she presented with progressive fatigue and early onset of menopause, Lee et al. (2004) identified compound heterozygosity for mutations in the HJV gene: G320V and cys321 to trp (C321W; 608374.0007). Pituitary insufficiency was diagnosed, and deeply pigmented skin, elevated serum iron, and total iron binding capacity, as well as transferrin saturation, were found. The patient had had 2 normal pregnancies, the last when she was 21 years old; she developed amenorrhea at age 23 years. Her medical history also included hypothyroidism treated with thyroxine for most of her adult life. She also had had multiple dental problems since early adulthood, requiring a dental implant. She developed type II diabetes (125853) at age 59 years, which was controlled by an oral hypoglycemic agent. In 17 patients with juvenile hemochromatosis (JH) from 12 families of the isolated region of Saguenay-Lac-Saint-Jean in Quebec, who were previously studied by Rivard et al. (2003), Lanzara et al. (2004) identified homozygosity for the G320V mutation. However, among 13 unrelated Italian JH patients in the study, the only G320V homozygote was likely of Greek ancestry, because he lived in a southern Italian region where a dialect resembling Greek was still spoken. In 6 of 7 patients with JH from 6 unrelated central European families (from Germany, Slovakia, and Croatia), Gehrke et al. (2005) identified homozygosity for the G320V mutation in 4 patients and compound heterozygosity for G320V and a 4-bp deletion (608374.0008) in 2 patients. Gehrke et al. (2005) concluded that the genetic background of JH might be more homogeneous than initially believed. In a Croatian patient who had the most severe phenotype, with liver cirrhosis, severe dilated cardiomyopathy, and hypogonadism, Gehrke et al. (2005) also found a heterozygous C282Y mutation in the HFE gene (613609.0001) and suggested that HFE mutations might influence the phenotypic expression in HJV-related JH. In a 21-year-old male patient with hemochromatosis who died due to low cardiac output and multiorgan failure, Brakensiek et al. (2009) identified homozygosity for the G320V mutation in the HJV gene, as well as compound heterozygosity for the H63D (613609.0002) and S65C (613609.0003) mutations in the HFE gene. Brakensiek et al. (2009) suggested that severity of the clinical course in this patient might be related to the complex genotype. (less)

In 7 of 10 Greek families with juvenile hemochromatosis (HFE2A; 602390), Papanikolaou et al. (2004) identified a homozygous gly320-to-val (G320V) mutation in the HJV gene. Affected individuals shared the common Greek haplotype. This same mutation was found in 1 Canadian and 1 French family with juvenile hemochromatosis. In 1 Greek family, the G320V mutation was in compound heterozygous state with arg326 to ter (R326X; 608374.0002), and in 1 Canadian family, G320V was in compound heterozygous state with ile222 to asn (I222N; 608374.0003). In a white female diagnosed with hereditary hemochromatosis (HFE1; 235200) at the age of 30 years when she presented with progressive fatigue and early onset of menopause, Lee et al. (2004) identified compound heterozygosity for mutations in the HJV gene: G320V and cys321 to trp (C321W; 608374.0007). Pituitary insufficiency was diagnosed, and deeply pigmented skin, elevated serum iron, and total iron binding capacity, as well as transferrin saturation, were found. The patient had had 2 normal pregnancies, the last when she was 21 years old; she developed amenorrhea at age 23 years. Her medical history also included hypothyroidism treated with thyroxine for most of her adult life. She also had had multiple dental problems since early adulthood, requiring a dental implant. She developed type II diabetes (125853) at age 59 years, which was controlled by an oral hypoglycemic agent. In 17 patients with juvenile hemochromatosis (JH) from 12 families of the isolated region of Saguenay-Lac-Saint-Jean in Quebec, who were previously studied by Rivard et al. (2003), Lanzara et al. (2004) identified homozygosity for the G320V mutation. However, among 13 unrelated Italian JH patients in the study, the only G320V homozygote was likely of Greek ancestry, because he lived in a southern Italian region where a dialect resembling Greek was still spoken. In 6 of 7 patients with JH from 6 unrelated central European families (from Germany, Slovakia, and Croatia), Gehrke et al. (2005) identified homozygosity for the G320V mutation in 4 patients and compound heterozygosity for G320V and a 4-bp deletion (608374.0008) in 2 patients. Gehrke et al. (2005) concluded that the genetic background of JH might be more homogeneous than initially believed. In a Croatian patient who had the most severe phenotype, with liver cirrhosis, severe dilated cardiomyopathy, and hypogonadism, Gehrke et al. (2005) also found a heterozygous C282Y mutation in the HFE gene (613609.0001) and suggested that HFE mutations might influence the phenotypic expression in HJV-related JH. In a 21-year-old male patient with hemochromatosis who died due to low cardiac output and multiorgan failure, Brakensiek et al. (2009) identified homozygosity for the G320V mutation in the HJV gene, as well as compound heterozygosity for the H63D (613609.0002) and S65C (613609.0003) mutations in the HFE gene. Brakensiek et al. (2009) suggested that severity of the clinical course in this patient might be related to the complex genotype. (less)