Small-platelet thrombocytopenia in a family with autosomal recessive inheritance pattern.

We describe the clinical and laboratory features of a family of Arab ancestry and consanguinity. Five affected individuals were diagnosed in two sibships. All affected members have small platelets, severe to moderate thrombocytopenia of neonatal onset, increased bleeding tendency and bleeding complications such as: life-threatening massive hemoperitoneum due to corpus luteum rupture during ovulation and severe mucosal bleeding. The familial involvement and early onset of the disease support the presence of a congenital genetic disorder with an autosomal recessive inheritance pattern. This does not fit the clinical spectrum of any of the currently known thrombocytopenia disorders.

Genetic heterogeneity in two consanguineous families segregating early onset retinal degeneration: the pitfalls of homozygosity mapping.

Retinitis pigmentosa is the most common form of hereditary retinal degeneration, with a worldwide prevalence of 1 in 4,000. At least 28 genes and loci have been implicated in nonsyndromic autosomal recessive retinitis pigmentosa. Here we report two extended and highly consanguineous families segregating early onset retinitis pigmentosa. Despite the consanguinity in both families, we found allelic heterogeneity in one of them, in which affected individuals were compound heterozygotes for two different mutations of the CRB1 gene. In the second family we found evidence for locus heterogeneity. A novel homozygous mutation of RDH12 was found in only 14 of 17 affected individuals in this family. Our data indicate that in the other affected individuals the disease is caused by a different gene/s. These findings demonstrate that while homozygosity mapping is an efficient tool for identification of the underlying mutated genes in inbred families, both locus and allelic heterogeneity may occur even within the same consanguineous family. These observations should be taken into account, especially when studying common and heterogeneous recessive genetic conditions.