Another disorder finds its gene

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Siintola et al . describe for the first time three patients with a deficiency of the lysosomal aspartyl proteinase cathepsin D (CTSD). In one of these patients, the authors found a mutational inactivation of the cathepsin D gene ( CTSD ) that encodes CTSD. All the patients described had severe neurological abnormalities at birth including intractable seizures, spasticity, apnoea and microcephaly. This deficiency is proposed as the underlying cause of congenital neuronal ceroid lipofuscinosis (CNCL) (Humphreys et al ., 1985; Garborg et al ., 1987; Barohn et al ., 1992). Originally described in a sheep model (Tyynela et al ., 2000, 2001) and further corroborated by findings in a canine model (Awano et al ., 2006), defects in CTSD were considered to be part of the neuronal ceroid lipofuscinoses (NCLs). The ovine model proved to be a feasible tool to study the disease. The affected sheep have a mutation in the active site of CTSD and newborn lambs suffer similar pathological and neurological consequences as seen in the human NCLs. The NCLs encompass a group of lysosomal storage diseases sharing similar clinical features (Goebel et al ., 1999; Herva et al ., 2000; Santavuori et al ., 2000; Weimer et al ., 2002; Mole, 2004). Described in the 19th and early 20th century as one disease with a variable age of onset, these diseases are now known to be caused by mutations in six different genes ( CLN1 – CLN3 , CLN5 , CLN6 and CLN8 ) located on different chromosomes (for a review see Mole, 2004). Adult NCL is expected to be caused by mutations in a gene not yet identified ( CLN4 ). The worldwide incidence of the NCLs is 1 : 30 000 live births (Santavuori et al ., 2000). The NCLs present with …