| #613235 | ||||||||||||||||||
| FACTOR XIII, B SUBUNIT, DEFICIENCY OF | ||||||||||||||||||
| Phenotype Gene Relationships | ||||||||||||||||||
| ||||||||||||||||||
| Clinical Synopsis | ||||||||||||||||||
| TEXT | ||||||||||||||||||
| A number sign (#) is used with this entry because deficiency of factor XIII (F13) subunit B is caused by mutation in the F13B gene (134580) on chromosome 1p. See also deficiency of factor XIII (F13) subunit A (613225), which is caused by mutation in the F13A gene (134570) on chromosome 6p. | ||||||||||||||||||
| Description | ||||||||||||||||||
| Factor XIII deficiency is an autosomal recessive hematologic disorder characterized by increased bleeding and poor wound healing. Most cases of congenital factor XIII deficiency result from mutation in the A subunit (Kangsadalampai et al., 1999). Ichinose et al. (1996, 2000) proposed a classification of factor XIII deficiency: XIIIA deficiency (formerly 'type II' F13 deficiency) and XIIIB deficiency (formerly 'type I' F13 deficiency), as well as a possible combined deficiency of the 2. | ||||||||||||||||||
| Clinical Features | ||||||||||||||||||
| Saito et al. (1990) reported a 32-year-old Japanese woman with deficiency of subunit B of factor XIII. It was not clear if she had bleeding from the umbilical stump after birth, as is commonly observed in F13 subunit A deficiency. During childhood, she showed occasional subcutaneous bleeding, but had no abnormal bleeding after a caesarean section at age 26. At age 31, she showed massive vaginal bleeding during a second pregnancy and abnormal bleeding after caesarean section. A sister reportedly had severe hemorrhage after 2 pregnancies. Laboratory studies showed low F13 activity (24%) in the proband, her sister (less than 10%), and her clinically unaffected brother (10%); subunit B levels were undetectable in the proband and her brother, whereas subunit A levels were normal in the proband and very low in the brother. (The subunit levels were not tested in the sister.) Heterozygous levels of subunit B activity (34 to 52%) were observed in her unaffected parents and her children. The findings were consistent with a primary deficiency of subunit B. Saito et al. (1990) further concluded that the deficiency only becomes clinically apparent when an obstetric event or surgery overlaps with a deficiency, as the brother had no history of a bleeding diathesis. The trait was consistent with autosomal recessive inheritance. Koseki et al. (2001) reported 2 unrelated Japanese patients with factor F13B deficiency. They were identified by postoperative bleeding in one, and umbilical bleeding in the other. Plasma F13 activity levels were less than 10% of control values. Immunoblot analysis showed complete lack of F13B in the patients. In the first patient, the F13A was significantly decreased to about 12% of normal; in the second patient, plasma F13A was approximately 40%, although it varied between 5% and 40% through his neonatal period. These results indicated that both patients had primary F13B deficiency. Koseki et al. (2001) suggested that the complete lack of F13B resulted in a secondary loss of F13A because of the innate instability of the F13A molecule. However, the clinical symptoms of F13B deficiency may be milder than that of F13A deficiency since residual catalytic F13A activity remains. Although F13B deficiency may be more difficult to ascertain, it appears to be an extremely rare condition. | ||||||||||||||||||
| Molecular Genetics | ||||||||||||||||||
| In a Japanese patient with complete absence of the B subunit of factor XIII reported by Saito et al. (1990), Hashiguchi et al. (1993) found compound heterozygosity for 2 mutations in the F13B gene (134580.0001 and 134580.0002). In 2 unrelated Japanese patients with F13B deficiency, Koseki et al. (2001) identified homozygous and compound heterozygous mutations in the F13B gene, respectively (134580.0001 and 134580.0005). | ||||||||||||||||||
| REFERENCES | ||||||||||||||||||
| ||||||||||||||||||
| ||||||||||||||||||