ABSTRACT
Importantly, for MC, a century of hypotheses on the nature of membrane pores and their contribution to cellular electrical activity led eventually to the accidental discovery of muscle-type Cl− channels in the electroplaque of Torpedo californica (White and Miller, 1979). Rapid advances took place once the electroplaque Cl− channel gene had been cloned (Jentsch et al., 1990). Almost immediately, a whole group of related mammalian (and human)
Contents 41.1 Introduction 611 41.2 CLC-1 (202 variations in the CLCN1 gene associated with disease) 613
41.2.1 Myotonia congenita, omsen disease (MIM 160800) 613 41.2.2 Recessive generalized myotonia, Becker disease (OMIM 255700) 614 41.2.3 Myotonic dystrophy 1, Steinert disease (MIM 160900) and myotonic dystrophy 2, proximal myotonic
myopathy (PROMM), Ricker syndrome (MIM 602668) 617 41.2.4 Epilepsy? 617
41.3 CLC-2 (23 variations in the CLCN2 gene-disease association not conrmed) 617 41.4 GLIALCAM (HEPACAM) (15 variations in the HEPACAM gene associated with disease) 618
41.4.1 Megalencephalic leukoencephalopathy with subcortical cysts 2A and 2B (MLC2A and MLC2B) (MIM 613925 and 613926) 618
41.5 CLC-Ka (2 variations in the CLCNKA gene associated with disease) 618 41.6 CLC-Kb (74 variations in the CLCNKB gene associated with disease) 618
41.6.1 Bartter syndrome type 3, classical Bartter syndrome (MIM 607364) 618 41.6.2 Gitelman syndrome (MIM #263800) 619 41.6.3 Bartter syndrome 4B, infantile Bartter syndrome with sensorineural deafness (MIM 613090) 619
41.7 Barttin (17 variations in the BSND gene associated with disease) 619 41.7.1 Bartter syndrome 4A (MIM 602522) 619 41.7.2 Rarely, deafness occurs with only mild renal dysfunction 619
41.8 CLC-3 (No CLCN3 variations have been associated with any human disease) 620 41.8.1 Neuronal ceroid lipofuscinosis? Cardiovascular disease? Glioma? 620
41.9 CLC-4 (No CLCN4 variations have been associated with any human disease) 620 41.10 CLC-5 (140 variations in the CLCN5 gene have been associated with disease) 620
41.10.1 Dent disease 1 (MIM 300009) and related allelic disorders 620 41.11 CLC-6 (No CLCN6 variations have been associated with any human disease) 621
41.11.1 Neuronal ceroid lipofuscinosis? Cardiac disease? 621 41.12 CLC-7 (65 variations in the CLCN7 gene associated with disease) 621
41.12.1 Albers-Schönberg disease, AD osteopetrosis 2 (MIM 166600); infantile malignant osteopetrosis 2, AR osteopetrosis 4 (MIM 611490) 621
41.13 Ostm1 (4 Variations in the OSTM1 gene associated with disease) 622 41.13.1 Infantile malignant osteopetrosis 3, AR osteopetrosis 5 (MIM 259720) 622
41.14 Conclusions 622 References 622
PROTEIN, (GENE) TISSUE
DISTRIBUTION
MEMBRANE (PROTEIN
FUNCTION) DYSFUNCTION
WHEN MUTATED
NATURALLY OCCURRING
ANIMAL MODELS,
(KNOCKOUT MOUSE) HUMAN DISEASE
ClC-1a (CLCN1) Skeletal muscle Sarcolemma, t-tubule membrane? (Cl-ion channel)
Membrane voltage instability
Myotonic adr mouse; myotonic goat, dog, horse, bualo, etc.
