Homozygous TBCE Gene Mutation c.155-166del in a Libyan Patient with Sanjad-Sakati Syndrome: Same Gene Mutation Responsible in All Arab Ethnic Patients.

Sanjad-Sakati syndrome (SSS) (Online Mendelian Inheritance in Man 241410) is a rare autosomal recessive disorder also known as hypoparathyroidism-retardation-dysmorphism syndrome. It is characterized by congenital hypoparathyroidism, growth retardation, typical facial features, and variable developmental delay. SSS is caused due to mutations of the tubulin-specific chaperone E ( TBCE ) gene. In this article, we reported the first Libyan child of first parental consanguinity with SSS and whole exome sequencing results identified the homozygous missense variant c.155-166del and it encodes p.(Ser52-Gly55del) (chr1:235564867) located in the TBCE gene , chromosome 1q42.3. In addition, the patient was also diagnosed with congenital hypothyroidism and presented with acquired bilateral cataract in the first year of life. Most likely, all Arab patients with SSS syndrome have the same TBCE gene mutation.

Further evidence supporting the role of DUT gene in diabetes with bone marrow failure syndrome.

In 2017, a homozygous DUT mutation was reported to cause a syndrome of diabetes and bone marrow failure. However, no further patient with this combination has been reported and the phenotype of heterozygous DUT mutation is unknown. We describe the genotype, phenotype, and post bone marrow transplantation (BMT) data of two unrelated families with this rare syndrome. Whole-exome and/or direct sequencing of the DUT gene were performed in all family members. Each family has two children presented within the first 10 years of life with thrombocytopenia, macrocytosis, with or without anemia, followed by non-autoimmune diabetes. The same homozygous missense DUT mutation, reported in 2017 (c.425A>G p.(Tyr142Cys), was detected in all affected children. The heterozygous carriers have no BM failure, one developed type 2 diabetes, and the rest have normal fasting glucose, insulin, HbA1c, and c-peptide. Multiple nevi were detected in homozygous and heterozygous mutation carriers. Allogenic BMT normalized BM aplasia without impact on diabetes. Post BMT follow-up revealed normal puberty and school performance; but three have height <2.5 SDS. We add two families with this syndrome supporting a role of DUT in bone marrow and ß-cell function. The heterozygous carriers of this DUT mutation appear to be healthy.