ClinVar

Shwachman-Diamond Syndrome 1

For discussion of the splice site mutation in the SBDS gene (IVS2DS+2T-C) that was found in compound heterozygous state in patients with Shwachman-Diamond syndrome (SDS1; 260400) by Boocock et al. (2003) and Kuijpers et al. (2005), see 607444.0001. Boocock et al. (2003) referred to this mutation as 258+2T-C.

Nakashima et al. (2004) identified this mutation in affected members of 4 Japanese families with SDS, making it the most prevalent mutation. Recurrent gene conversion was considered the most likely explanation for the recurrence, rather than founder effect.

Aplastic Anemia, Susceptibility to

Calado et al. (2007) identified heterozygosity for the IVS2DS+2T-C mutation in 4 of 91 unrelated patients with aplastic anemia (609135). These patients were younger on average (5 to 19 years) compared to other patients with aplastic anemia. Two mothers tested were carriers of the mutation; these 2 and another mother who was not tested had histories of subclinical mild anemia. Heterozygous mutation carriers had partial loss of SBDS protein expression, indicating haploinsufficiency. Although telomere shortening was observed in patients' granulocytes, lymphocytes had normal telomere length. None of the patients with aplastic anemia had pancreatic exocrine failure or skeletal anomalies as seen in SDS. One of the 4 probands was also heterozygous for a presumed pathogenic variant in the TERT gene (187270).