NMMHC-A mutational analysis.

(A) Affected or unaffected individuals are represented by filled or open symbols, respectively. Mutation status indicated by −, wild-type homozygote; +, mutant heterozygote. (B) The portions of the representative electropherograms illustrate the 5 heterozygous nucleotide changes. Forward sequence is shown from families IN, HI, and IT, and reverse sequence from families MA, MU, and KO. In each panel, the normal sequence is shown at the top, and the mutated sequence is shown at the bottom. The mutated position is indicated by arrows. (C) Schematic representations of 41 exons of NMMHC-A are shown at the top, and the predicted amino acid of NMMHC-A at the bottom. The amino terminal globular head domain is shaded and the carboxyl terminal rod domain is not. The transcription initiation codon (ATG), natural stop codon (TAA), ATP-binding domain and actin-binding domain are indicated. (D) NMMHC-A sequence alignment. Amino acid sequence alignment is shown from the 2 human NMMHC isoforms and the known NMMHC from the other species. The amino acid alterations in each of the 6 families are indicated in bold. D1424N, D1424H, E1841K, and R1933X mutations occur at highly conserved residues of the protein. In family MA, 5779delC mutation causes a frameshift and a premature termination at 20 amino acids downstream of the mutation.