A recessive contiguous gene deletion of chromosome 2p16 associated with cystinuria and a mitochondrial disease

Deletions ranging from 100 Kb to 1 Mb-too small to be detected under the mi croscope-may still involve dozens of genes, thus causing microdeletion synd romes. The vast majority of these syndromes are caused by haploinsufficienc y of one or several genes and are transmitted as dominant traits. We identi fied seven patients originating from an extended family and presenting with a unique syndrome, inherited in a recessive mode, consisting of cystinuria , neonatal seizures, hypotonia, severe somatic and developmental delay, fac ial dysmorphism, and lactic acidemia. Reduced activity of all the respirato ry chain enzymatic complexes that are encoded in the mitochondria was found in muscle biopsy specimens of the patients examined. The molecular basis o f this disorder is a homozygous deletion of 179,311 bp on chromosome 2p16, which includes the type I cystinuria gene (SLC3A1), the protein phosphatase 2C beta gene (PP2C beta), an unidentified gene (KIAA0436), and several exp ressed sequence tags. The extent of the deletion suggests that this unique syndrome is related to the complete absence of these genes' products, one o f which may be essential for the synthesis of mitochondrial encoded protein s.